Systems for delivering anti-infective compositions to treat disordered tissue such as cold sores

ABSTRACT

The present invention relates to the treatment of disordered epithelial tissues such as cold sores and other complications resulting from disorders such as herpes, and the like. The invention relates to the use of an anti-infective and/or antimicrobial active agent in a carrier, with vigorous agitation of the disordered epithelial tissue for topical treatment thereof under such conditions sufficient to achieve clinically discernable improvement of the disordered epithelial tissue. The preferred anti-infective and/or antimicrobial active agent is an organohalide such as a quaternary ammonium compound, preferably benzalkonium chloride. The inventive method may be used also in connection with a preferred applicator configuration.

RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 09/401,076 which was filed on Sep. 22, 1999 for B. Ron Johnsonnow U.S. Pat. No. 6,211,243. The amended title of Ser. No. 09/401,076 isMETHODS FOR TREATING COLD SORES WITH ANTI-INFECTIVE COMPOSITIONSDELIVERED WITH VIGOROUS AGITATION. For purposes of disclosure of thepresent invention, Ser. No. 09/401,076 is incorporated herein byspecific reference.

BACKGROUND OF THE INVENTION

1. The Field of the Invention

The present invention relates to the treatment of disordered tissue withanti-infective compositions especially antiviral and antimicrobialcompositions. More particularly, the treatment compositions includequaternary amine medicament compounds or organochlorides. The presentinvention provides a novel combination of treatment compositions andmodes of applying them to treat tissue disorders, particularlyepithelial tissue disorders such as herpes infections.

2. The Relevant Technology

Tissue disorders, particularly those which impact epithelial tissue suchas Herpes Simplex types I and II, candida albicans, acne, psoriasis,eczema, seborrhea, dermatitis, and pink eye are common and are oftendifficult to treat symptoms. Such disorders are more likely to developin people living with compromised sanitary conditions, the elderly, andthe chronically ill. Others susceptible to such disorders includeworkers in health care, agricultural workers, chemical industry workers,individuals working with industrial cleaners, and painters, wherechronic exposure to chemicals, pathogens, and unsanitary conditions tendto weaken and irritate epithelial tissue.

Herpes simplex virus (HSV) and Herpes Zoraster, commonly referred to as“herpes virus” or “herpes,” is an infectious disease which has reachedcrisis proportions nationally with estimated numbers of infected peopleat 70%-80% of U.S. population as reported by the American Social HealthAssociation (ASHA) and growing annually by 500,000 people or more. Thereare two common types of herpes: herpes simplex virus 1 (HSV 1) andherpes simplex virus 2 (HSV 2).

Herpes enters the human body through minuscule breaks in the epidermaltissue usually by contact with an infected host and is marked byeruption of one or more vesicles, usually in groups, following anincubation period of approximately four to ten days. Typically thecourse of the infectious outbreak initiates with the prodromal stage;advancing to vesicular eruption; followed by: ulceration; coalescing;resolution; and the latency period. The outbreak can last for severalweeks and on average lasts two to three weeks. In some immunecompromised individuals, the outbreak can last for months. The vesiclescan appear anywhere on epithelial tissues including the skin or mucosa,typically appearing on the lips as cold sores, glands, oral mucosa,conjunctiva and cornea, genitalia, anal mucosa and perianal tissue.

Herpes symptoms include: inguinal swelling, pain, fever, malaise,headaches, muscle aches, and swollen glands. Some individuals with oralherpes which impacts the trigeminal nerve, have excruciating facialpain, difficulty swallowing, eating and facial swelling. Individualswith the herpes which impacts the sacral nerve have severe upper legpain, swelling, and great difficulty walking.

Herpes simplex virus (HSV) infection is recurring, residing in the nerveganglia, then recurring due to some, as yet unknown, stimulus. Recurrentherpetic infections can be precipitated by almost anything, including:overexposure to sunlight; nutritional deficiencies; stress;menstruation; immunosuppression; certain foods; drugs; febrile illness;etc.

Herpes infections pose very serious health threats often causing:blindness; increased cancer risk of the cervix; aseptic meningitis andencephalitis; neonatal deaths; viremia; the spread of the humanimmunodeficiency virus (HIV); etc. The devastating effects of thisdisease, go well beyond the medical scope of human suffering; HSV isresponsible for serious psychological and emotional distress as well assubstantial economic loss.

Various treatments for herpes have been proposed and have includedtopical application of such agents as povidone-iodine, idoxuridine,trifluorothyidine, or acyclovir. Such treatments have met with varyingdegrees of success. Most prior treatments have proven disappointing.Acyclovir, an acyclic nucleoside, is taken orally for systemic treatmentof HSV. Acyclovir is somewhat effective in inhibiting the activity ofseveral herpes viruses. However, acyclovir is only successful ininterrupting the replication of the virus and is used to treatinfectious outbreak systemically. Denever is the topical version ofacyclovir. Nothing to date has proven really effective topically.Strains resistant to acyclovir have been reported. Individuals with AutoImmune Deficiency Syndrome (AIDS) are seriously immune-compromised andsuffer especially debilitating outbreaks of HSV. Additionally, AIDSindividuals may carry acyclovir resistant strains of HSV, which can makeacyclovir ineffective for these individuals. It is, therefore, of utmostimportance to develop a safe and successful medical treatment toovercome the very serious problems of herpes virus.

Biologically active antiviral and microbial compositions have been metwith marginal success when administered topically for tissue disorders.Such compositions have been applied as gels, creams, lotions, oils,ointments, pastes, tinctures, emulsions, and colloidal suspensions. Mostof the compositions are oil-based to ensure that the composition hassufficient viscosity and/or tackiness to remain on the surface of theskin. In fact, such compositions are generally absorbed into clothingmore than into the skin due to a relatively slow epidermal penetrationrate. Even when applied to patients and time is available for thecompositions to penetrate, they often were not sufficiently effectivefor one reason or another to substantially assist them in clearing upthe disorder. Note that the FDA restricts the over-the-counter sellingof compositions that do not remain on the surface of the skin forextended periods of time.

Many efforts have been undertaken to remedy the inadequate results oftopically administered compositions having antiviral and antimicrobialqualities. The therapeutic effects of such compositions depend upon thespecific active agent and the method of application. Many compositionsof the prior art contain ingredients that may provide symptomatic reliefof pain and itching, but none are claimed to be effective against Herpesinfection except the drug, acyclovir, which is purported to have sometopical efficacy. Additionally, most compositions intended to treat suchdisorders do not effectively treat the discomfort and the diseasesymptoms, let alone cure the disorder or put it into a significantremission.

Examples of conventional application methods and compositions areprovided in WO 98/42188 and in WO 98/11778 by Squires, both of which arehereby incorporated by reference. In WO 98/42188 at page 9, lines 12-18and in WO 98/11778 at page 5, lines 22-30, it is stated that thecomposition is applied by “spraying, dabbing, dusting, swabbing,sponging, brushing, pouring, dispensing, covering or heavily coating.”The stated objective of these techniques for applying the composition isto insure that the composition remains on the infected area. Like otherconventional treatment compositions, the composition has a viscosityand/or tackiness which enables it to remain on the surface of theinfected area. A portion of such compositions may eventually penetratebeyond the surface of the disordered tissue such as the outer surface ofskin or a lip, however, the viscosity of the composition combined withthe application technique prevents such compositions from achievingeffective penetration.

Another example of conventional application methods and compositions isprovided in U.S. Pat. No. 5,753,270 issued to Beauchamp et al., which isalso incorporated by reference. U.S. Pat. No. 5,732,270 discloses acomposition which includes: (a) an antiseptic and/or anesthetic compoundwhich is (i) a terpene such as menthol or eucalyptol, (ii) a phenoliccompound such as thymol, or (iii) an alcohol such as menthol; (b) aquaternary ammonium antiseptic compound such as benzethonium chloride;and (c) an antiseptic compound containing iodine, salts thereof and/orcomplexes thereof dissolved in an organic skin penetrating solvent suchas a mixture of water and acetone. The methodology is described in theexamples provided at columns 5-7 as involving the liberal application ofthe composition to the afflicted area in a sequence such as 3 to 4applications over a one minute period which is then repeated every 3minutes over a 10 minute period. The entire procedure is then repeatedafter approximately ½ to 1 hour for 2 to 3 hours or until activity isstopped in healing is evident. The use of a cotton swab is mentioned atcolumn 6, lines 10-11 for applying the composition.

Although it is mentioned in U.S. Pat. No. 5,753,270 at column 3, lines44-49 that the formulations may be prepared as a gel, cream, a lotion,an ointment, or a paste the preferred embodiment appears to be asolution having an aqueous solvent system. It is noted at column 3,lines 6-9 that although use of water and acetone as a solvent ispreferred such a solvent is not considered essential to the overallsynergistic action of the formulation. In any event, the formulationappears not to rely on either its viscosity or tackiness to ensure thatthe formation is maintained on the surface of the afflicted area as domost conventional compositions. Rather the methodology involves the veryfrequent reapplication of the formulation to the afflicted area. Some ofthe formulation may be absorbed into the skin, however, a significantportion is likely rapidly evaporated due to the high content of waterand acetone.

The active agents disclosed in U.S. Pat. No. 5,753,270 which arediscussed above include at least one compound which is an antisepticand/or an anesthetic. The primary examples of such compounds: menthol,eucalyptol, and thymol are either obtained from natural sources such asnaturally occurring oils or are derived from such oils. Eucalyptol isdescribed as being an essential oil and a terpene ether. Thymol isderived from thyme oil or other oils. Menthol is obtained frompeppermint oil or other oils. Other suitable compounds are also recitedin the claims as including: eugenol, camphor, hexetidine or anethol.While the basis for inclusion of hexetidine in this grouping is notclear, the other chemicals are also obtained from natural sources or arederived therefrom. Eugenol is obtained by extraction of clove oil andthen chemical modification. Camphor is a ketone which occurs naturallyin the wood of the camphor tree. Anethol is derived from anise or fenneloils. While these compounds are useful, particularly as antifungalagents, it is doubtful that they assist in penetrating the afflictedtissue and may in fact retard or enhance the skin's natural resistanceto penetration. The FDA does not consider these compounds as useful inthe treatment of herpes, rather they are used for their softeningeffects.

In conclusion, significant medical research in this field of endeavorhas been focused on developing compositions used for treating affectedtissues and yet compositions which provide rapid relief to theseailments are still needed. It would therefore be an improvement in theart to provide a method of treating tissue disorders such as epithelialtissue disorders that overcome the problems of the prior art.

Such methods and systems of application are taught and claimed herein.

SUMMARY AND OBJECTS OF THE INVENTION

The present invention relates to the treatment of disordered tissue suchas cold sores. An applicator may be used to apply a treatmentcomposition comprising an anti-infective active agent in a carrier. Themethod may include vigorously agitating the disordered tissue treatmentsite with the applicator under conditions which are sufficient to enablethe anti-infective active agent to rapidly penetrate the disorderedtissue.

The present invention relates to the treatment of tissue disorders suchas infections, particularly herpes related cold sores or other herpesdisordered tissue. Throughout this disclosure, use of the term“disordered tissue” or “afflicted tissue”, is understood to representall tissue which has been affected by disorders such as, cold sores, allHerpes, candida albicans, acne, psoriasis, eczema, seborrhea,dermatitis, pink eye, shingles, and other predominantly viral disorders.Microbial and fungal infections are also types disordered tissues.Additionally, disordered tissue includes tissue which has been infectedby venom as results from snake and spider bites, particularly venominfections from Brown Recluse spiders and Black Widow spiders.

It has been found that the therapeutic irritation of disordered tissuewith a preferred, treatment composition and the optional use of anapplicator, stimulates rapid immunological attack and makes thecomposition and therapeutic irritation synergistically more effective.After the therapeutic irritation of the disordered tissue throughvigorous rubbing and/or pressure, the treatment composition penetratesinto the disordered tissue to enable the anti-infective active agent oragents to become chemically active much more deeply within thedisordered tissue as compared to conventional application techniques.

In addition to the anti-infective active agent or agents, thecomposition also includes a carrier such as an alcohol. Oil and fattycarrier substances are preferably not added to the composition. Althoughvarious compositions have been applied to disordered tissue, theinventive methods and systems of vigorous irritation of the disorderedtissue in connection with a preferred composition has extraordinarytherapeutic effects. Consequently, the inventive compositions as well asthe methods of application with vigorous irritation of disordered tissueprovide effective methods of treatment.

The inventive systems utilize an applicator to deliver the treatmentcomposition and most of the applicators can also be utilized tovigorously irritate disordered tissue to convey the inventivecomposition into the disordered tissue. The applicators allow thepatient or a health professional to vigorously irritate the disorderedtissue without cross-contamination from a dirty finger or the like. Afinger may be used, of course, but it lacks the advantages of a sterileapplicator, the absorbability of an applicator tip and the ability toirritate the skin surface in the desired manner. The applicator has theadded advantage of directing focused pressure into the disordered tissuewhile the active compounds are expressed from the applicator into thedisordered tissue. The combined effect of vigorous irritation of thedisordered tissue and the administration of the inventive treatmentcompositions has the remarkable result of surprising therapeuticeffects. Note that oils on the finger may react with the active agentand lessen its impact in the disordered tissue. For this same reason,moisturizing lotions should preferably not be applied to the treatmentarea after application of the treatment composition.

It is therefore an object of the present invention to provide a methodfor treating disordered tissue such as disordered portions of skin andmucous membranes. It is therefore an object of one embodiment of thepresent invention to provide a system for the treatment of epithelialtissue disorders that includes a preferred biologically anti-infectiveactive composition and an applicator in connection with delivering thetreatment composition and also preferably vigorously irritating thedisorder site.

These and other objects and features of the present invention willbecome more fully apparent from the following description and appendedclaims, or may be learned by the practice of the invention as set forthhereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

In order that the manner in which the above-recited and other advantagesand objects of the invention are obtained, a more particular descriptionof the invention briefly described above will be rendered by referenceto specific embodiments thereof which are illustrated in the appendeddrawings. Understanding that these drawings depict only typicalembodiments of the invention and are not therefore to be considered tobe limiting of its scope, the invention will be described and explainedwith additional specificity and detail through the use of theaccompanying drawings in which:

FIG. 1 is a vertical cross-section of the epidermis and the papillae ofthe dermis;

FIG. 2A is an exploded perspective view of a preferred applicator thatcontains the treatment composition;

FIG. 2B is a perspective view of the preferred applicator depicted inFIG. 2A as it appears assembled prior to use;

FIG. 2C is a perspective view of the preferred applicator depicted inFIG. 2B after the glass reservoir is crushed and the treatmentcomposition is allowed to permeate the agitation pad;

FIG. 2D is a perspective view of an individual applying the treatmentcomposition according to the present invention;

FIG. 2E is a detail taken along the section line 5—5 that depicts aclose-up view of the inventive method;

FIG. 2F schematically shows an embodiment of a pad that can be used toapply the treatment composition according to this invention.

FIG. 3 is an elevational cross section view of an applicator that has afinger loop for vigorous topical irritation of the treatment site;

FIG. 4 is an elevational side view of an alternative applicator used inthe present invention,

FIG. 5 is an elevational side view of an alternative applicator that isfixed to a digit for vigorous topical irritation of the treatment site;and

FIG. 6 is a cross-sectional plan view of an alternative applicator thatis placed over a digit and that is contained in a pre-wetted statebefore use.

FIG. 7 is a perspective view with a partial break-away view of analternative applicator that is used to apply the treatment compositionto large surface areas of the body.

FIG. 8 is a perspective view of the alternative applicator in FIG. 7being used to apply the treatment composition to sores from shingles onthe chest area.

FIG. 9 is a perspective view of a towelette being used to apply thetreatment composition to a cold sore.

FIG. 10 is a perspective view of a towelette being used to apply thetreatment composition to a sore on male genitalia.

FIG. 11 is a perspective view of a towelette being used to apply thetreatment composition to sores from shingles on the chest area.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention relates to the treatment of disordered tissue withcompositions that are any one or all of antiviral, antimicrobial,antifungal, or antivenomous. The compositions are rapidly absorbed intothe disordered tissue. The efficacy of the compositions in penetratingthe disordered tissue and initiating the restoration of the disorderedtissue is enhanced by vigorously irritating the disordered tissue site.The disordered tissue is preferably vigorously agitated with anapplicator. This is remarkably efficacious in causing the compositionsto penetrate into disordered tissue and to stimulate the immuneresponses. Whether the anti-infective compositions are merely deliveredonto the disordered tissue or delivered with vigorous irritation of thedisordered tissue, the results are surprisingly advantageous in thetreatment of epithelial tissue disorders.

Hereinbelow is a discussion of what is meant by vigorous irritation ofdisordered tissue, followed by a detailed description of the treatmentcomposition. The description of the treatment composition is followed bya detailed description of several embodiments of applicators. FIGS.2A-2F depict a preferred applicator. Other embodiments of applicatorsare shown in FIGS. 3-8. FIGS. 9-11 depict towelettes being used. FIG. 1depicts a cross-sectional view of skin.

The phrase “vigorous agitation” means that the skin is irritated in amanner that allows the inventive compositions to penetrate below thesurface of the skin, preferably to a nerve ending. As described in moredetail hereinbelow, such vigorous agitation is achieved through eitherapplying an appropriate amount of pressure for an adequate period oftime and/or appropriate rubbing for an adequate period of time. Vigorousagitation is preferably a combination of both adequate pressure andrubbing.

A suggested theory for the effectiveness which results from vigorouslyagitating the disordered tissue is set forth below. However, it shouldbe understood that the objective in vigorously agitating the disorderedtissue includes moving the tissue to better enable the treatmentcomposition to physically move through the layers of the disorderedtissue by moving the cells and fluids in the disordered tissue. Also,another objective of vigorous agitation is to stimulate the immuneresponses.

Vigorous agitation achieved through applying appropriate pressure may beunderstood to be an amount of pressure such that, where tissue overliesbone, the tissue is depressed to be firmly against the bone. Similarly,if the disordered portion of the tissue is adjacent to teeth or gumssuch as the skin around the mouth, then the disordered tissue issufficiently compressed due to the pressure that the pressure is felt onthe opposing surfaces within the mouth. Additionally, if disorderedtissue located around a patient's lip is also opposite the patient'sgums then pressure applied to the disordered tissue would also be feltat the portion of the patient's gums opposite the disordered tissuethrough the lip or cheek.

Vigorous agitation achieved though rubbing involves repeated movement ofthe applicator in a frictional manner with the disordered tissue. Forexample, the applicator may be moved in a steady back and forth motionon the disordered tissue or rotated as the treatment composition isapplied or after delivery of the composition. As described in greaterdetail in reference to the applicator, the applicator is preferablyconfigured to provide a relatively uniform abrasive action. Theoscillation rate of the back and forth motion depends on several factorssuch as the amount of pressure being simultaneously applied and thecondition of the disordered tissue. So in some instances the oscillationrate may be only 1 stroke every few seconds while in other circumstancesthe oscillation rate may range from about 1 strokes per second to about10 strokes per second. More typically, however, the oscillation rate isin a range from about 2 strokes per second to about 6 strokes per secondand is most typically in a range from about 3 strokes per second toabout 4 strokes per second. Note that the portion of the applicator usedto rub the disordered tissue preferably has a size in a range from about50% to about 200% the size of the disordered tissue treatment site. Forexample, it has been found that a contact surface that is about 8 mm indiameter is useful for agitating most cold sore treatment sites.

The length of time that vigorous agitation of this type may be sustainedupon a disordered tissue treatment site may vary according to theindividual, the size of the applicator surface in relation to the sizeof the disordered tissue to be agitated, the amount of pressure appliedas defined above and the oscillation rate of the rubbing. As the lengthof time increases in which the applicator delivery surface is maintainedin contact with the disordered tissue, the required pressure decreasesfor achieving the desired penetration of the treatment composition intothe disordered tissue. Typically, the vigorous agitation is maintainedfor at least 1 second and is more typically maintained for a fewseconds. However, the period of time may range from about 3 seconds toabout 1 minute depending on the condition of the disordered tissue, theamount of pressure being applied and/or the movement of the applicator.Vigorous agitation is most typically maintained for a period of time ina range from about 5 seconds to about 15 seconds.

The intensity of the vigorous agitation is adjusted depending on thethickness of the skin. For example, the tissue on a lip that must bepenetrated is much thinner than that of the skin on the arms, legs, andchest. The thickness is even greater for the skin on the palms of handsand feet and is still greater for other body parts such as backs. So itmay be necessary to vigorously agitate the disordered tissue withgreater intensity when treating sores on a patient's chest or backcaused by shingles then the vigorous agitation is required to treat acold sore on one's lip.

It is counterintuitive to vigorously agitate disordered tissue such as acold sore as the disordered tissue already hurts so one inherentlydesires to avoid even contacting such sensitive disordered tissue.However, patients are likely to be more tolerant of any pain which mayresult from vigorous agitation when bolstered by knowledge that vigorousagitation significantly enhances the ability of the treatmentcompositions disclosed herein to effectively penetrate disorderedtissue.

Vigorous agitation need not necessarily be painful, although, vigorousagitation may also be understood to mean that discomfort is felt by thepatient beyond nominal dabbing of the disordered tissue as with othertreatments that call for gentle application to the disordered tissue.Before a cold sore has erupted, and is in the prodromal stage orvesicular stage such that at most there is merely a vistule, it may notbe painful to vigorously agitate the disordered tissue. However, whenvigorously agitating disordered tissue which is in an erupted stage, theagitation may be sufficient to cause sharp pain and bleeding.

Obviously however disordered tissue such as cold sores cannot always bevigorously agitated. As indicated above, when a cold sore is in theprodromal stage it can be vigorously agitated without significantsensitivity. However, when the cold sore has become an open sore lesspressure may be utilized so as to minimize the potential for causingpain. Also, if the cold sore has coalesced then it is best not tovigorously agitate the treatment site as such action is likely todisturb the coalesced tissue, scab, etc. Also, when treating sensitiveareas such as inside the mouth, mucous coated tissues, the eyes,genitalia, etc. the treatment composition should be applied withoutvigorous agitation.

As indicated above, the vigorous agitation can also be defined bycontrasting it with nominal dabbing of the disordered tissue whichinvolves the mere application of a treatment composition. The same islikewise true for other application techniques such as swabbing,sponging, and brushing merely to ensure that a treatment composition isapplied or delivered. Dabbing and other application techniques do notinvolve pressing hard enough such that the disordered tissue iscompressed against a bone or such that pressure is felt as a surface inthe mouth opposite the disordered tissue is pressed against teeth orgums. Mere application of a treatment composition such as nominaldabbing of the disordered tissue does not cause bleeding of thedisordered tissue, for example, if it is a cold sore in an eruptedstage.

Despite a patient's desire to enable disordered tissue to return tonormal some patients are also likely to adjust the amount of pressureapplied or the rate of rubbing in order to experience minimal pain.However, as indicated above, it is not necessary for a patient to feelpain in order for the treatment composition to be delivered withvigorous agitation. The objective is to move the tissue somehow eitherthrough compressing the tissue through the application of an appropriateamount of pressure as discussed above for an adequate period of timeand/or by rubbing the tissue in manner such that tissue is moved aroundfor an adequate period of time for the treatment composition topenetrate such that it does not remain on the surface.

The treatment composition is preferably absorbed into the disorderedtissue to such an extent that within several minutes after applicationthe composition can no longer be seen. This is absorption or penetrationrate is achieved either with or without vigorous agitation. Morepreferably, the composition is not visibly detectable within 2 minutesafter being applied and is most preferably not visibly detectable within1 minute after being applied. Note that the content of the compositionhas different formulations, however, in the preferred embodiment thereis no residue remaining after the composition has been applied andabsorbed which is visibly detectable.

As indicated above, the treatment composition preferably penetratesthrough the skin to a nerve ending or causes a penetration sensation atthe nerve ending. The pathway for this penetration is discussed ingreater detail below with reference to FIG. 1. After the composition isdelivered with simultaneous agitation, the penetration or thepenetration sensation preferably occurs within about one minute. Thepenetration or penetration sensation to a nerve ending is morepreferably achieved in about 30 seconds and most preferably in less thanabout 10 seconds. In more serious cases when the disordered tissuerepresents an extensive problem, several treatments may be used insteadof a single, primary treatment. Note that when several treatments areused instead of a single, primary treatment, it is preferable to use aclean and sterile applicator for each repeated treatment.

FIG. 1 is a vertical cross-section of the epidermis and the papillae ofthe dermis. FIG. 1 illustrates the stratum corneum 28 disposed upon thefatty layer or stratum lucidum 30. The stratum lucidum is disposed overthe stratum granulosum 32. Below the stratum granulosum 32 is thestratum spinosum 34. Typically, the stratum spinosum 34 has a lipid filmdisposed around each individual cell. Below the stratum spinosum 34 isthe stratum basale 38 that overlies vascularized tissue. Within thevascularized tissue the nervous papilla of the corium 36 is locatedalong with blood vessels and nerves 40. FIG. 1 shows the treatmentcomposition being delivered to the stratum corneum 28 in order to allowtreatment composition 22 to penetrate therethrough. The treatmentcomposition is shown being delivered from an impregnated agitation pad12 accompanied by vigorously rubbing.

The arrows illustrate directions of agitation movement by way ofnon-limiting example. Note, however, that FIG. 1 does not depict theapplication of pressure as the objective in FIG. 1 is to show theparticular layers involved in their natural positions and once pressureis applied the layers are moved from their natural positions. Althoughthe inventor does not wish to be bound to a single theory, it ispostulated that treatment composition 22 may move through the stratumcorneum 28 without significant rupture thereof due to the vigorousagitation by impregnated agitation pad 12. Treatment composition 22 canpenetrate to the nervous papilla of the corium 36 by the combination ofvigorous agitation and the penetrating nature of the carrier.Preferably, vigorous agitation and the combination of the penetratingquality of the carrier are sufficient conditions to cause theanti-infective active agent to penetrate the disordered tissue to anerve ending such as the nervous papilla of the corium 36.

Note that the application of pressure further increases the ability ofthe treatment composition to penetrate as the pressure may flatten orcompress the layers and may assist in forcing the treatment compositiondownward. In any event, under the inventive conditions, penetration tothe nerve ending is rapidly accomplished, preferably in several seconds.

While the treatment composition 22 rapidly penetrates to the nerveendings, it is also postulated that the treatment composition resides inreservoir amounts within the stratum spinosum 34 and may continue todiffuse across the stratum basale 38 to the nerve endings over anextended period of time. Vigorous agitation may assist in displacingfluid held within the stratum spinosum which is then replaced with thetreatment composition. When the stratum spinosum 34 is filled with thetreatment composition then the treatment composition is available as abath that continues to provide protection as it slowly diffuses. On thisbasis, it is preferred to deliver a large quantity of the treatmentcomposition on the disordered tissue such that the stratum spinosum 34is saturated in the region of the cold sore or other disordered tissuefor a period that enables the treatment composition to achieve itspurpose before it diffuses into the body. For example, the volumeapplied to a typical cold sore may be in range from about 0.2 ml toabout 1 ml, preferably in range from about 0.4 ml to about 0.8 ml and ismost preferably about 0.6 ml. Low amounts of volume, such as about 0.2ml, work for a single cold sore especially if the applicator does notretain a significant portion of the volume however the volume ispreferably greater. In order for all of the volume to be delivered, halfof the total volume in the applicator may be delivered and then theremainder may be delivered. Delivery of such large volumes is discussedbelow in reference to the applicators used to deliver the treatmentcomposition.

The treatment compositions include at least a biologically active agentand a carrier. The biologically active agent is able to be effective instopping tissue disorders such as cold sores, as the carrier is selectedto optimally enable the treatment composition to penetrate. Thebiologically active agents suitable for use in the treatmentcompositions are set forth hereinbelow and then the carriers aredescribed. Other optional components are also described.

The biologically active agents or anti-infective agents included in theanti-infective treatment compositions are preferably anti-infectiveorganohalides, especially anti-viral organohalides. Benzalkoniumchloride is the preferred organohalide. However, other organohalides orquaternary ammonium compounds may be used as the active agents in thecompositions. Other active agents that are organohalides may includeorgano-bromides and organo-iodides. Preferably, the organohalides havean alkyl group attached thereto such as a simple C_(n)H_(2n+1) chain,where n is in a range from 1 to about 50.

The chemical structure of benzalkonium chloride is shown below:

wherein R=C₈H₁₇ to C₁₈H₃₇. As shown, benzalkonium chloride includes abenzene ring and a nitrogen constituent bound to the ring by a carbonatom. Two methyl groups and an R group of varying size extend from thenitrogen atom. Suitable benzalkonium chloride may be obtained from manysuppliers for example, Spectrum of Gardena, Calif.; Stephan ofNorthfield, Ill.; Sanofit Pharmaceuticals, Inc. of New York, N.Y. andMason Chemical of Arlington Heights, Ill.

These anti-infective agents, particularly benzalkonium chloride, arehighly effective in limiting the source of infections and othercomplications related to disordered tissue. Also, these anti-infectiveagents destroy or eliminate toxins caused by substances such as viruses.Note that the toxins and their sources are rapidly eliminated to resultin almost immediate pain relief.

While the active agents include organohalides, most suitableorganohalides are organochlorides. Benzalkonium bromide is an example ofa suitable organohalide which is not an organochloride. Benzalkoniumbromide has the structure of benzalkonium chloride with the differencethat the chlorine is substituted with a bromine radical. Another exampleof a suitable organohalide which is not an organochloride is cetyltrimethylammonium bromide.

Other organochlorides which have anti-infective properties and aresuitable for use as the anti-infective organochloride in the treatmentcomposition include: benzethonium chloride, methyl benzethoniumchloride, cetyl pyridinium chloride, chloroxylenol, hexachlorophene,triclosan, chlorhexidine. Note that some of the above organochloridesare not suitable for all purposes. For example, benzethonium chloridecannot be used in a manner which would enable it to be ingested in atoxic quantity as it is potentially toxic if ingested. Similarly, theconcentration of benzalkonium chloride must not be excessively high.

Additional examples of other organochlorides which may be suitable, moreparticularly quaternary ammonium chlorides having an alkyl with 6-18carbons, include:

alkylbenzyldimethylammonium chloride, alkyldimethyl/ethylbenzylammoniumchloride, n-alkyldimethylbenzylammonium chloride,diisobutylphenoxyethoxyethyldimethylbenzylammonium chloride,n-(C₁₂C₁₄C₁₆)alkyl dimethylbenzylammonium chloride,didecyldimethylammonium chloride, dioctyldimethylammonium chloride,dialkyldimethylammonium chloride, dialkylmethylbenzylammonium chloride,octyldecyldimethylammonium chloride, lauryldimethylbenzylammoniumchloride, o-benzyl-p-chlorophenol, dideryldimethylammonium chloride,dioctyldimethylammonium chloride, alkyl(C₁₄C₁₂C₁₆)dimethylbenzylammoniumchloride. In addition to these organochlorides, other knownantimicrobial agents may also be used as the active agent or incombination with the active agents provided above. For example,chemicals which are known to act as an antiviral, antibacterial orantifungal agents such as the antifungal agents disclosed by Chodosh inU.S. Pat. Nos. 5,661,170 and 5,827,870, which are hereby incorporated byreference. It is also possible that a chemical such as acyclovir may beeffective as an anti-infective agent when delivered with the carriers asdisclosed herein combined with vigorous agitation. So in contrast to theconventional understanding that acyclovir is ineffective when topicallyapplied, it may be useful as an anti-infective agent when used as taughtherein. Note, however, that acyclovir is not an organohalide and so maynot be as easily absorbed into the skin or penetrate as readily.However, to the extent that acyclovir, related substances such asdenever, femiver or any other suitable anti-infective agent can bedelivered in the inventive compositions or in accordance with inventivemethodologies and systems, it is also within the scope of the presentinvention.

When the anti-infective agent is benzalkonium chloride, theconcentration is preferably in a range from about 0.01% to about 0.5% byvolume of the treatment composition, is more preferably in a range fromabout 0.05% to about 0.3% by volume of the treatment composition, andeven more preferably in a range from about 0.1% to about 0.2% by volumeof the treatment composition. Concentrations above 0.5% by volume areconsidered to pose potential toxicity problems, accordingly, theconcentration is preferably less than 0.26% and is most preferably about0.13% by volume of the treatment composition. Depending on theparticular, organohalide or quaternary ammonium chloride, theconcentration may vary. For example, the concentration may range fromabout 0.001% to about 2% by volume of the treatment composition.

For the specialized treatment of the eyes, an eyewash having the activeagent is made into a composition with an active agent concentration inthe volume range from about 0.001% to about 0.05%. Preferably, theactive agent concentration for an eyewash is in the range from about0.005% to about 0.03%. Higher concentrations may be administered by amedical professional. The specialized treatment of the eyes may alsorequire several treatments instead of a single, primary treatment. Whereeye drops are used, according to the inventive method, the compositionis deposited onto the eye and the patient closes the eye after the eyehas been contacted with composition, and the patient may opt to rub theeyeball through the eyelid to assist in the delivery of the treatmentcomposition and the penetration into the eye tissue. If the disorderedtissue is in a corner of the eye, it may even be vigorously agitated. Asubsequent treatment and a series of subsequent treatments may also becarried out on the eyes. As indicated above, the carrier is a vehiclefor the biologically active agent, more to particularly theanti-infective active agent. The carrier causes effective wetting of thetissue to be treated and then enables the anti-infective agent to movewithin this carrier into the disordered tissue.

In one embodiment, the treatment composition consists of only the activeagent such as benzalkonium chloride and the carrier. In otherembodiments, the treatment composition consists essentially of theactive agent and the carrier, however, other components may also beincluded as described hereinbelow. In any event, the carrier ispreferably sufficiently inert with respect to the active agent and anyother component present to enable the treatment composition to be storedfor long periods of time without deactivating the anti-infective agent,such as a 1 year period and preferably a 2 year period.

The carrier has properties which enhance the ability of the treatmentcomposition to penetrate into the disordered epithelial tissue. Moreparticularly, the carrier has a viscosity and/or density which is notsignificantly greater than that of water in order to optimally enablethe treatment composition to penetrate into the disordered tissue. Usinga carrier having a viscosity which is not significantly greater thanthat of water is in sharp contrast to conventional compositions whichenable the composition to be coated onto afflicted tissue. Accordingly,the treatment compositions specifically exclude formulations which maybe considered to be primarily or essentially gels, creams, lotions,oils, ointments, pastes, emulsions, and colloidal suspensions. Notehowever that small amounts of inert abrasive material may be present inthe treatment compositions as discussed hereinbelow. Note also thecarrier may include substances which have either a viscosity or densitywhich is more than slightly greater than that of water as long as othersubstances are also included in the carrier such that the mixture haseither a viscosity or density which is not significantly greater thanthat of water.

The carrier preferably has a tissue penetrating component such asisopropyl alcohol that is capable of penetrating the skin in a rapidmanner without rapidly diffusing beyond the skin into the body. Moreparticularly, the carrier preferably enables the stratum spinosum 34 tobe saturated in the region of the cold sore or other disordered tissuefor a period that enables the treatment composition to achieve itspurpose before it diffuses into the body.

The carrier may be formed from a single liquid constituent such asisopropyl alcohol or water as described hereinbelow, or from more thanone constituent. Although, water alone may be used as the carrier, it isnot preferred because other compounds, such as some alcohols, have atissue penetrating capability that water does not have. The carrier inthe treatment composition is also preferably not formed entirely from analcohol such as isopropyl alcohol or ethyl alcohol, since their use maybe more painful in some circumstances. More particularly, when an opensore is part of the disordered tissue, the amount of alcohol or othercomposition that has a significant tissue penetrating ability may bemodified by adding water so as to moderate the amount of discomfort thatthe patient experiences by the application of the composition to theopen sore. Additionally, the evaporation rate of a carrier that includesalcohols such as isopropyl alcohol can be reduced by including water.Further, it may be preferred to use alcohols such as isopropyl alcoholwith other constituents such as water due to regulatory issues. Alsosome substances, such as benzylkonium chloride, dissolve best in acarrier that includes water.

While isopropyl alcohol is a preferred carrier due to its ability toeffectively penetrating tissue, other alcohols may also be used. Inaddition to isopropyl alcohol, ethanol, and methanol are also suitablecarriers. Benzyl alcohol can be used as a carrier or as an additive asit also acts as a bacteriostat and an anesthetic. Mixtures of theabove-mentioned alcohols are also preferred depending upon theapplication. As indicated above, however, isopropyl alcohol or ethylalcohol is preferably used in combination with other carrierconstituents. For example, as mentioned above water may be added toisopropyl alcohol to reduce the pain which may be felt when onlyisopropyl alcohol is used. Similarly, isopropyl alcohol may be utilizedwith cetyl alcohol or with a combination of both cetyl alcohol and waterto reduce the sensation.

As noted above, the carrier preferably has a tissue-penetratingconstituent such as isopropyl alcohol. It has been noted that theability of the treatment composition to penetrate disordered tissue issignificantly enhanced when at least a portion of the carrier isisopropyl alcohol. While not being limited by any particularly theory,it is suggested that isopropyl alcohol opens cells and is not blocked bylipids or lipid layers in the disordered tissue. Accordingly, it isbelieved that isopropyl alcohol penetrates so effectively due to itsability to remove lipids from the tissue. The penetration ability of acarrier comprising isopropyl alcohol may be further enhanced byincluding a very small amount of ethyl alcohol such that the carrier isless than about 1% ethyl alcohol.

As indicated above, the preferred carrier includes isopropyl alcohol andwater. As also discussed above, isopropyl alcohol is included in thecarrier for its ability to rapidly penetrate disordered tissue while thewater is included primarily to minimize the sensation which may be feltas the isopropyl alcohol penetrates the skin. While substances likelidocaine and other substances that have anesthetic qualities can beused instead of water to reduce the sensation caused by isopropylalcohol, the carrier preferably includes water with the isopropylalcohol as benzalkonium chloride dissolves more easily in such acombination than in isopropyl alcohol alone. It is also simpler to use acarrier that includes both isopropyl alcohol and water than it is topretreat the disordered tissue with an anesthetic composition. However,pretreating the disordered tissue with an anesthetic composition is alsowithin the scope of the present invention.

Carriers that include isopropyl alcohol and water have varying ratiosdepending on the intended use. However, for treating cold sores thewater is preferably included in a range from about 10% to about 50% byvolume of the carrier with the remainder being isopropyl alcohol. Thewater content is more preferably in a range from about 20% to about 40%by volume of the carrier. The most preferred carrier for treating coldsores is a carrier wherein water is included in an amount of about 30%by volume of the carrier and wherein the isopropyl alcohol is includedin an amount of about 70%. Although, these ranges of water content areprovided based on the volume of water in the carrier, essentially thesame water contents apply to the overall treatment composition since theother active agent and any other optional component are typicallyincluded in such small amounts. For example, the most preferredcomposition is a treatment composition including about 0.0133%benzalkonium chloride by volume of the treatment composition, 29.987%water by volume of the treatment composition and 70% isopropyl alcoholby volume of the treatment composition.

When treating sensitive parts of the body such as the genitalia andadjacent areas, the carrier may include isopropyl alcohol in an amountof about 10 to about 15% by volume of the carrier and water in an amountof about 85% to about 90%. However, as noted above, higherconcentrations can still be used even in sensitive areas, particularlywhen pretreated with an anesthetic composition.

While rapid penetration is desired, it should be understood that theobjective is rapid penetration to the nerve ending without thereafterrapidly passing through the skin and into the blood stream. Accordingly,the carrier preferably does not include substances or at least not largequantities of substances such as dimethyl sulfoxide (DMSO) as suchsubstances immediately penetrate the skin and enter the blood stream.

The carrier may also include acetic compounds such as acetone, aceticacid, acetic anhydride, and the like. However, if acetone and the likeare used they are preferably used in small quantities and not as thesole constituent as they evaporate to rapidly and do not penetrate aswell as isopropyl alcohol. While some acetic compounds may not be aseffective as certain alcohols, particularly isopropyl alcohol, acetonedoes exhibit some ability to penetrate tissue. So although aceticcompounds such as acetone may be used alone it is preferably used incombination with other substances. One preferred carrier combination isethanol and acetone in a ratio of about 70% ethanol by volume of thecarrier, preferably 80% ethanol and most preferably about 90% ethanolwith 10% acetone by volume of the carrier. As mentioned above withrespect to the water content for carriers formed from water and alcohol,the ratios provided for combinations of ethanol and acetone based on thevolume of the carrier apply also to the volume of the treatmentcomposition.

The above carriers may also be combined across class lines. As such, thecarriers such as water, alcohols, and acetic compounds may be combined.One example is water, alcohol, and acetone in respective amounts of 30%,60%, and 10%, by volume of the carrier. Generally speaking, theconstituents may be combined in any suitable ratio such as: 1:1:0,1:2:0, 1:10:0, 1:1:1, 1:2:1, 1:10:1, 1:10:10, and 1:2:10.

As indicated above, the carrier is preferably a liquid that includesalcohol as it is believed that alcohols included in sufficient quantityto act as the carrier may have the quality of removing lipids from thetissue and thereby enabling the active agent to move within thedisordered tissue. It is also believed that the ability of the treatmentcomposition to penetrate the disordered tissue is hindered by includingcomponents in the composition such as oils or materials which havetraditionally been included to enable the composition to be coated ontothe surface of the disordered tissue. Examples of such materials includepetrolatum which is used in various cold sore treatment compositions.For example, the popular over-the-counter lip ointment sold under thetrademark BLISTEX by Blistex Incorporated of Oakbrook, Ill. 60521. TheBLISTEX ointment contains allantoin (1%), camphor (0.5%) and phenol(0.5%) in an emollient base with petrolatum, lanolin, menthol, methylsalicylate, and other ingredients. Other widely used ingredients whichare included to increase the viscosity or to increase the tackinessincludes polyethylene glycol and polypropylene glycol. An example of aproduct which utilizes polyethylene glycol and polypropylene glycol is agel sold under the trademark ORAGEL MOUTH AID by Del LaboratoriesIncorporated of Farmingdale, N.Y. 11735. Other thickeners are taught inU.S. Pat. No. 5,661,170, which was previously incorporated by reference,as including cellulosic materials and waxes. In addition to petrolatumbased materials and thickeners, it is also believed that materials whichare either obtained from natural sources such as naturally occurringoils present in trees, bushes, plants, etc. or substances which arederived from such oils may also reduce the ability of the treatmentcomposition to penetrate the disordered tissue. Such materials arereferred to herein as penetration inhibiting components.

As indicated above, penetration inhibiting components include chemicalswhich are petrolatum based substances, materials conventionally utilizedas thickeners, naturally occurring oils, substances derived fromnaturally occurring oils or any other substance which is added primarilyto increase the tendency of a treatment composition to remain on thesurface of disordered tissue such as a cold sore. Note that whilesubstances such as petrolatum or thickeners are not added individually,a component may be added which includes minute amounts of naturallyoccurring oils or substances derived from oils obtained from naturalsources. So although, the inventive composition is preferablysubstantially oil free, the term “substantially oil free,” is meant thatoil substances are preferably not individually added, but may be presentdue to the natural content of a substance added to the inventivecomposition. As such, oil may be incidentally present in an amount ofless than about 2% by volume, and is preferably incidentally present inan amount of less than about 0.1%, and is most preferably incidentallypresent in an amount less than about 0.02% and even more so at an amountless than about 0.01%. Additionally, in some instances it may bedesirable to add very small quantities of naturally occurring oils orsubstances, however, the concentration is no more than the incidentalamounts discussed above.

Note that penetration inhibiting components, are believed to act as abarrier which seals in toxic irritating by-products of viral growth.They prevent the natural weeping process of the disordered tissue whichflows to remove toxins, etc. Accordingly, use of such penetrationinhibiting components causes more damage to the disordered tissuedespite the temporary advantages achieved though using such substances.

As indicated above, the treatment composition may consist of only theactive agent and the carrier. Treatment compositions consistingessentially of the active agent and the carrier do not includepenetration inhibiting substances but may include other components addedfor specific purposes. These components or additives are added toachieve a particular result and do not have a substantial impact on theability of the treatment composition to penetrate into the disorderedtissue or the ability of the treatment composition to be anti-infective.Examples of such components are additives which are conventionally usedas preservatives, pH adjusters, substances having anesthetic qualities,vasodilators, analgesics and defoamers. These components or additivesare used in concentrations which correspond with amounts conventionallyutilized.

Generally, preservatives may be added to the anti-infective composition.Examples of preferred preservatives include parabens, preferably themethyl and propyl parabens. Preferably the preservatives, if present,are supplied to the composition in a range from about 0.0001% to about0.01% by volume of the treatment composition.

Additives such as those set forth above can be blended with otheringredients to make up the inventive composition including pH adjustors.Such pH adjustors may include organic acids, mineral acids in minuteamounts, organic bases or mineral bases also in minute amounts.Preferred organic acids include citric acid, ascorbic acid, sorbic acid,malic acid, ascetic acid, succinic acid, caproic acid, and the like.Other preferred acids include hydrochloric acid, nitric acid, hydroiodicacid, and the like in minute amounts. Preferred bases include methyl andethylamines such as triethanolamine, and the like. Other preferred basesinclude, ammonium hydroxide, potassium hydroxide, sodium hydroxide, andthe like.

The inventive compositions may include compounds with anestheticqualities. Depending upon the application site, whether on dermal layersor on mucous membranes, different anesthetics may be preferred. Oneparticularly preferred anesthetic is benzocaine. Benzocaine isespecially useful in the areas of open sores such as cold sores, eczemasores, and the like. Of the amides, such compounds as bupivocaine,carbocaine, and ropivocaine may be preferred. Of the esters, suchcompounds as procaine, cocaine, novocaine tetracaine and benzocaine maybe preferred. Other preferred anesthetics include alkaloids such ascocaine, caffeine, nicotine, xylocaine, and the like. Another preferredanesthetic includes a combination of lidocaine and prilocaine. Withthese two compounds, an eutectic mixture is achieved with a meltingpoint below room temperature. A preferred composition of the lidocaineand prilocaine is about 2.5% each in a 1:1 mixture. Other preferredanesthetics include oil of cloves, tea tree oil (melaleuca alternifolia,which also acts as a disinfectant) and the like. Other preferredanesthetics include lidocaine hydrochloride, dibucaine, dibucainehydrochloride, tetracaine hydrochloride, tronothane, dyclonine,dyclonine hydrochloride, pramoxine hydrochloride, diperodon, butambenpicrate, cyclomethycaine sulfate, cyclomethycaine hydrochloride, anddimethisoquin hydrochloride. Where an anesthetic is present, it issupplied to make up the composition in a range from about 0.001% toabout 0.01% by volume of the treatment composition.

Other preferred components for the inventive composition includevasodilators such as nitroglycerine and the like. Vasodilators areuseful for causing penetration of the active agent or agents into thedisordered tissue to its base in the skin or mucous membranes an beyond.Care must be taken to balance the effect of localized vasodilationagainst the systemic toxicity of the inventive composition such thatpenetration into the disordered tissue is clinically significant, butthat the active agent or agents remain substantially local to thedisordered tissue for maximum efficacy. Where a vasodilator is suppliedto make up the inventive composition, it may be provided in a preferredrange from about 0.001% to about 0.05% by volume of the treatmentcomposition.

Other preferred components for the inventive composition includeanalgesics such as methyl salicylate, aspirin, and other salicylatesalts. Other preferred components for their analgesic effects includeN,N-dimethyl aspartic acid; N-N-dimethyl glutamic acid, trolaminesalicylate, antipyrine, and salicylamide. Where an analgesic is present,it may be supplied to make up the composition in a preferred range fromabout 0.001% to about 0.01% by volume of the treatment composition.

Most of the active agents disclosed above are considered to be cationicsurfactants so it is generally unnecessary to include any surfactants.It is also generally unnecessary to include surfactants as the treatmentcomposition is substantially oil free. Additionally, the active agentcan be used with various carriers so the carrier can be modified toachieve optimal solubility as needed. To the extent that a surfactant isincluded, for example, to assist in tissue wetting properties, thesurfactants may be anionic, cationic, or nonionic, and amphoteric. Insome circumstances it may be useful to use other surfactants such as:another cationic surfactant, an ampholytic surfactant or a zwitterionicsurfactant. U.S. Pat. No. 5,661,170, referenced above, may be referredto for a disclosure of suitable surfactants.

Abrasives are generally not necessary as a component of the compositionas the applicators are configured for abrasion. Additionally, whenirritating an open sore it would be undesirable for abrasives to bedeposited into the open sore. Nor is it generally necessary to includeabrasives on the applicators, which also risks the abrasives beingdislodged from the applicator and into an open sore. However, this doesnot exclude the use of abrasives as free-floating inert components in atreatment composition nor their surface attachment to or impregnation inan applicator. If used, suitable abrasives may include pumice and thelike as well as oxides such as alumina, silica, mica, zirconia, titania(both anatase and rutile), and the like.

In making a mixture of any of the preceding carriers and additives, itis understood that the recitation of compounds as mixtures includes thesolution and reaction products thereof. A preferred method for preparingthe inventive composition is to dissolve the anti-infective active agentinto the carrier, such as to dissolve benzalkonium chloride in isopropylalcohol. In general, it is only necessary to mix the agent, such asbenzalkonium chloride, into the carrier. In some instances, it may behelpful to first lower the pH of the solution into a range preferred toassist the dissolution of selected components. Note that benzalkoniumchloride is alkaline. Following dissolution of the selected componentsthat are assisted in their dissolution by a lower pH, the solution maybe either warmed or the pH increased, or both, and other components maybe added, preceding or following the warming and/or the pH increase.

The use of soap is preferably avoided in the inventive method as ittends to significantly reduce the efficacy of the methodology. However,the inventive method may include a precleaning step that compriseswashing the disordered tissue treatment site. The precleaning step mayinclude the use of a pre-moistened, organohalide impregnated towelette.Commercially available towelettes are preferably not used as thesetowelettes contain components which are generally considered undesirablein combination with the present invention. Accordingly, when aprecleaning towelette is used, it is preferred that the towelette bemoistened with a composition which does not contain any penetrationinhibiting components such as lanolin. An example of a commerciallyavailable towelette is the PDI® towelette made by ProfessionalDisposables, Inc. of Orangeburg, N.Y. which is impregnated withbenzalkonium chloride. Another example is the WET ONES® towelette madeby Playtex Products, Inc. of Dover, Del. which is pre-moistened,benzethonium chloride impregnated towelette.

In one method of the present invention, a topical anesthetic may beapplied to the treatment site and enough time may be allowed to elapsein order to substantially anesthetize the nerve endings for disorderedtissue and surrounding tissue at and near the treatment site. Forexample, towelettes may also be used that are impregnated withanesthetics to reduce the sensitivity of an area that is to be treatedwith vigorous agitation. After sufficient anesthetization of thetreatment site, the inventive method continues by providing theinventive composition that contains the anti-infective agent followed byimpregnating an applicator with the composition, or using apre-impregnated applicator. Finally, the disordered tissue at thetreatment site is vigorously agitated with the applicator whilecontacting the disordered tissue with the composition. According to thisalternative inventive method, where a patient may have a low thresholdof pain tolerance, the preliminary anesthetization of disordered tissueat and near the treatment site allows for the vigorous irritation of thedisordered tissue without the accompanying discomfort.

Another alternative includes the application of a substance in liquidform in order to provide both sterile and cosmetic covering of thedisordered tissue after the inventive vigorous agitation treatment. Oneexample of a suitable liquid is NEW-SKIN® Liquid Bandage made by MedtechLaboratories, Inc. of Jackson, Wyo.

Applicators are preferably part of the inventive method and system. Assuch, applicators may be preconfigured with particular mixtures to treatspecific disorders such as cold sores, eczema, and the like. Applicatorsare well known in the art. Examples thereof include those taught byBooras et al. in U.S. Pat. No. 5,709,866; by Fox in U.S. Pat. No.5,704,906; by Mythling in U.S. Pat. No. 5,527,534; by Stalcup et al. inU.S. Pat. No. 5,016,651, by Bedford in U.S. Pat. No. 4,887,994; and byKorteweg in U.S. Pat. No. 4,952,204; the disclosures of which areincorporated herein by specific reference. Preferred applicators includeprepackaged applicators that have agitation pads impregnated with theinventive composition. An applicator may be provided as a unitarystructure such as a sealed container that is frangible and configuredfor a single use.

Applicators are preferably configured to enable the treatmentcomposition to be either delivered with vigorous agitation or to bemerely delivered onto the disordered tissue. Such flexibility is usefulsince tissue disorders such as cold sores typically progresses in stagesthat have varying pain thresholds. Whether the applicator is designed tovigorously agitate the disordered tissue or not, the applicator ispreferably able to deliver large volumes of the treatment compositiononto the disordered tissue. The delivery of large volumes of thetreatment composition may be achieved in several different ways.Applicators are also disclosed, however, that can only hold relativelysmall quantities of the treatment composition.

FIGS. 2A-2E depict a preferred applicator 10. The details of applicator10 are best seen in FIG. 2A which is an exploded perspective view, FIG.2B a perspective view of the assembled applicator and FIG. 2C as itappears when ready for application. Applicator 10 includes an absorbent,agitation pad 12, that is abutted against a is frangible ampule orreservoir 14 via open delivery end 17 of the flexible container 16.Frangible reservoir 14 is housed in a container 16 that forms a holderfor agitation pad 12. Frangible reservoir is enclosed by agitation pad12, the sidewalls of container 16 and the closed end 19 of container 16.Frangible reservoir 14 is preferably a thin glass ampule while container16 is preferably formed from a flexible plastic. A protective sleeve 18is provided that is designed to keep agitation pad 12 free fromcontamination until applicator 10 is ready for use on the disorderedtissue. A cap 20 is provided to fit into sleeve 18. The treatmentcomposition 22 is held in frangible reservoir 14 until such time asfrangible reservoir 14 is to be broken. One source for applicatorshaving a frangible reservoir and various pad configurations is JamesAlexander Corporation of Blairtown, N.J.

FIG. 2C is a perspective view of the preferred applicator depicted inFIG. 2B after frangible reservoir 14 has been ruptured. Treatmentcomposition 22 is allowed to permeate agitation pad 12 in preparationfor vigorous application to a disordered tissue treatment site. In FIG.2C, sleeve 18 has been removed to expose an impregnated agitation pad12. After impregnated agitation pad 12 is sufficiently wetted,application to the disordered tissue treatment site may commence.

FIG. 2D is a perspective view of an individual 26 applying treatmentcomposition 22 to a cold sore at or near the lip according to thepresent invention. FIG. 2D illustrates that sufficient pressure is beingapplied against a non-puckered lip as the lip is pressed against thepatient's teeth and/or gums in order to direct focused pressure into thedisordered tissue while the active compounds are expressed fromimpregnated agitation pad 12 and into the disordered tissue. Thecombined effect of vigorous irritation of the disordered tissue and theadministration of treatment composition 22 has the result of surprisingtherapeutic effects.

FIG. 2E is a detail taken along the section line 2E-2E in FIG. 2D thatdepicts a close-up view of the inventive method. The detail view moreclearly illustrates vigorous agitation of the disordered tissue sitewhere impregnated agitation pad 12 is being pressed into the lip inorder to be firmly felt at the gums or teeth opposite the disorderedtissue. The arrows illustrate directions of agitation movement by way ofnon-limiting example.

Pad 12 has several purposes. Once frangible reservoir 14 is ruptured thetreatment composition is delivered to pad 12 as gravity enables it toflow into pad 12, however, rupturing frangible reservoir 14 createsshards of glass. Pad 12 prevents these shards from passing and causinginjury as the pad is used to deliver the composition to the disorderedtissue. Another purpose of pad 12 is obviously the delivery of thetreatment composition so the pad has a certain mesh or configurationthat enables it to hold and deliver the treatment composition due toeither porosity, capillary action, etc. As discussed above in referenceto FIG. 2D, as pad 12 delivers the treatment composition it is alsopreferably used to vigorously agitate the disordered tissue.

Many configurations are available for a pad such as those disclosed inU.S. Pat. No. 1,822,566 and French Patent No. 2,700,698. The pad must ofcourse be configured to prevent the passage of shards of glass out ofcontainer 16 and to enable treatment composition 22 to be held anddelivered. The pad also preferably is configured for vigorouslyagitating the disordered tissue. Features that enable pad 12 to be usedin vigorously agitating the disordered tissue are discussed below.

Pad 12 is a folded sheet formed from a web of fibers. FIG. 2F depictssheet 12′ before it has been folded or collapsed to form pad 12. Asshown in FIG. 2F, the sheet has a fluted appearance in order to providean alignment such that when the sheet is gathered together in a bundle,it has longitudinal flutes. These longitudinal flutes provide a flowpath for treatment composition 22 while the interlocked web of fibersprevents the shards of glass from passing out of container 16. Pad 12has a configuration that is similar or identical to that of a cigarettefilter. Examples of cigarette filters configurations that may beutilized are disclosed in U.S. Pat. No. 5,465,739 and U.S. Pat.5,998,500, both of which are hereby incorporated by reference.

Pad 12 is preferably made of synthetic fibers that have a mesh whichenables it to hold treatment composition 22 while having sufficientroughness to allow vigorous or continual agitation of the disorderedtissue to enhance penetration by treatment composition 22. The fibersforming pad 12 are relatively densely positioned and are also relativelyrigid. The dense positioning and the rigid nature of the fibers enablesapplicator 10 to be used to vigorously agitate the disordered tissue.Note that applicator 10 is not used like a brush to merely apply thetreatment composition like conventional methodologies which involvecoating the afflicted tissue. If the fibers are relatively soft suchthat they flex significantly when pushed against the disordered tissuethen it is necessary to also push relatively hard against the disorderedtissue in order to insure that the disordered tissue has been adequatelyagitated. Accordingly, the fibers are preferably relatively rigidthrough either proper selection of the fiber material, the length of thefibers and/or the positioning of the fibers.

Pad 12 has a retention portion 13 positioned within flexible container16. Retention portion 16 is preferably attached to flexible container 16through use of an appropriate adhesive that remains inert in thepresence of the treatment composition or through heat fusing retentionportion 13 and flexible container 16 together. Pad 12 also has adelivery portion 14 opposite from retention portion 16 that extendsbeyond open delivery end 17 of the flexible container 16. Regardless ofthe configuration of pad 12 or the material from which it is formed, thedelivery portion is adapted to deliver the treatment composition to thedisordered tissue while vigorously agitating the disordered tissue toenhance penetration of the treatment composition into the disorderedtissue such that the treatment composition is no longer visiblydetectable on the disordered tissue within several minutes afterdelivery of the treatment composition onto the disordered tissue.

Delivery portion 17 terminates at an agitation surface 15 that isrelatively flat such that the disordered tissue is uniformly contacted.Uniformly contacting the disordered tissue with the flat surface reducesthe risk of injuring the disordered tissue as the disordered tissue isvigorously agitated. Use of such a pad is to be contrasted with the useof a pad having a delivery portion that is bulbous such as a swab usedin some applicators having a frangible ampule as disclosed in U.S. Pat.No. 1,822,566 and French Patent No. 2,700,698. A bulbous swab may tendto provide either insufficient contact when lightly pressed or unevenpressure when pushed hard enough to vigorously agitate the disorderedtissue. Although use of such a bulbous swab in place of a pad such aspad 12 may result in these disadvantages, such swabs may be used incertain circumstances.

The fibers used in pad 12 are preferably formed from polyester as suchpolyester fibers provide adequate stiffness at the desired length. Pad12 may also be formed from polyolefin, porous polyethylene or alaminated polyester foam. As used in the specification and the appendedclaims, the term “fibers” includes both synthetic fibers, inorganicfibers, naturally occurring organic fibers and treated organic fibers.As indicated above, synthetic fibers such as polyester fibers arepreferred. Another example of synthetic fibers includes polyethylenefibers. Polyethylene fibers having the same length and diameter aspolyester fibers are not as preferred as they tend be softer. Of coursethe abrasiveness of fibers can be increased by increasing the diameterof the fiber; however, it is preferred not to increase the diameter ofthe fibers as this results in a decrease in surface area for thetreatment composition to move downward on the fibers. Examples ofinorganic fibers include glass, silica, ceramic, graphite, metal fibers,and mixtures thereof. Any fiber which has the preferred physicalqualities such as strength, roughness, ability to hold liquids, and/orproper flexibility is also within the scope of the present invention.The only limiting criteria is that the fibers be able to be configuredin a manner that enables them to hold the treatment composition andagitate the afflicted tissue without adversely reacting with thechemical constituents of treatment composition 22. Examples of naturallyoccurring fibers, include cellulosic fibers extracted from abaca,bagasse, hemp, cotton, plant leaves, wood or sterns. The wood fibers maybe both hard wood or soft wood, such as southern pine. While pad 12 maybe made of such organic or naturally occurring fibers, it may benecessary to treat some naturally occurring fibers as discussedhereinbelow.

The retention portion of the pad has a length that is sufficient for thepad to be securely anchored in the open delivery end of the container.The delivery portion has a length and sufficient rigidity to enable theagitation surface to scrub the disordered tissue. When the pad is formedby folding or compressing together a sheet that is a polyester fiber webas shown in FIG. 2F at 12′, the retention portion preferably has alength ranging from about 5 mm to about 7 mm and the delivery portionpreferably has a length ranging from about 3 mm to about 5 mm. Thelength of the retention portion is more preferably about 6 mm and thelength of the delivery portion is more preferably 4 mm. However, theselengths depend on the particular material so the delivery portion maymerely range in length from about 1 mm to about 3 mm.

The diameter of the pad is preferably about 7 mm to about 1 cm, and ismost preferably about 8 mm. This diameter is sufficiently large toenable large amounts of treatment composition to be delivered andprovides sufficient surface area to contact a cold sore or otherdisordered tissue as need. More particularly, a pad diameter thatroughly corresponds with the diameter of a cold sore in its variousstages of development is ideally configured to vigorously agitate thecold sore treatment site.

In addition to a pad that is a folded sheet formed from a web of fibers,the pad may also be formed from a cluster of aligned bristles. Factorsrelated to selecting appropriate bristles include the rigidity andflexibility of the bristles based on the properties of the material usedto form the bristles, the length of the bristles especially the deliveryportion, and the diameter of the bristles. Another factor is thediameter of the cluster. All of these factors are balanced so that thecluster of aligned bristles enables the treatment composition to bedelivered while preventing passage of glass shards and so that thecluster of aligned bristles may be used in a scrubbing action. So whilethe cluster of aligned bristles may be held in place much like a brushand may be configured to brush the composition onto the disorderedtissue, the bristles are preferably sufficiently rigid for scrubbing thedisordered tissue as the treatment composition is delivered. Suchrigidity is preferably achieved through selecting a material, such asnylon, that is relatively rigid even when the bristle formed from thematerial has a relatively small diameter. Use of bristles havingrelatively small diameters is preferred to enable the cluster to scrubwhile minimizing any potential for injuring the disordered tissue. Forexample if the bristles are formed from nylon and are about 1 cm long sothat the retention portion and the delivery portion are each about 5 mmlong then the diameter may range from about 0.1 mm to about 0.2 mm, andis more preferably 0.15 mm

Note that the treatment composition flows more easily through a pad thatis a cluster of bristles than it does through a compressed sheet formedfrom a web of fibers. Also, less treatment composition is retained by acluster of bristles. Accordingly, the frangible ampule need not containas much treatment composition when the pad is a cluster of bristles.

An advantage of applicator 10 is that frangible reservoir 14 holds arelatively large volume of the treatment composition so that thetreatment composition is delivered in an amount that is relatively largecompared with the surface area to be treated. Further, the delivery israpidly achieved due to the design of applicator 10 without requiringrewetting of pad 12 as the treatment composition is continuallydelivered to pad 12 until it is all used. For example, frangiblereservoir 14 may deliver about 0.2 ml to about 1 ml to an area that isno greater than about 1 cm². Accordingly, the volume to surface arearatio is preferably in a range from about 0.2 ml/cm² to about 1 ml/cm².Such quantities are ideally sufficient to saturate the stratum spinosum34 in the region of the cold sore or other disordered tissue so that itis available as a protective bath around the nerve. In any event, thetreatment composition is preferably delivered in sufficiently largequantities that the disordered tissue at least appears moist andpreferably such that the treatment composition pools initially on thesurface of the disordered tissue. As indicated above, the penetratingcapabilities of the treatment composition enables it to be no longervisibly detectable on the disordered tissue within several minutes afterdelivery of the treatment composition onto the disordered tissue.

A suggested application procedure using applicator 10 is to apply the0.6 ml of the treatment composition for 30 seconds or longer, preferablywhile vigorously agitating the skin. Typical pain relief is withinminutes. It may also be advantageous, especially during the prodromalstage, to deliver half of the treatment composition while rubbing thecold sore or other disordered tissue for about 30 seconds, wait about 1minute and then deliver the remainder while rubbing for about 30 secondsagain. Typically a single application is all that is required peroutbreak, if the pain is not gone, or healing started in 24 hours thenthe treatment composition should be reapplied.

Another preferred applicator is illustrated in FIG. 3. FIG. 3 is across-sectional elevational view of an applicator 210 that may be partof the inventive system and method. Applicator 210 includes an absorbentagitation pad 212 that may be typical of a sterile adhesive bandage.Applicator 210 also includes adhesive wings 214 that may have adhesivetypical of a sterile adhesive bandage. A separate strip acts as acontainer 216 in order to cause treatment composition 22 to remain inagitation pad 212 until container 216 is stripped away from adhesivewings 214 of applicator 210. In addition thereto, a finger loop 228 thatmay include finger loop folds 230 and a finger loop tab 232 is attachedto applicator 210 immediately above agitation pad 212. Finger loop 228is configured to lie flat against adhesive wings 214 and can be openedby lifting on finger loop tab 232 and hinge open at finger loop folds230. Applicator 210 may be applied to a treatment site as typical of asterile adhesive bandage and left in place indefinitely. Additionally,after a selected time period of having applicator 210, particularlyagitation pad 212, upon a treatment site, the medical professional orthe patient may grab the adhesive wing tabs 234, and gently pulladhesive wings 214 away from the skin. Meanwhile, the medicalprofessional or the patient may insert a finger into finger loop 228,draw adhesive wings 214 also toward finger loop 228 and commence tovigorously agitate the disordered tissue.

Where it is preferable to immediately agitate the cold sore, applicator210 may be applied at the point of agitation pad 212 onto the disorderedtissue and then vigorously agitated against the disordered tissue.Thereafter, applicator 210 may be discarded or adhesive wings 214 may beapplied to the patient's skin to allow applicator 210 to remain over thedisordered tissue. This alternative may be preferable where bleeding isincidental to the inventive method. As such, applicator 210 doubles asan adhesive sterile bandage.

In summary, applicator 210 may be used for vigorous irritation of thedisordered tissue or merely as a delivery applicator. It may be usedinitially for application of the anti-infective active agent withoutvigorous irritation of the disordered tissue which is then followed byvigorous irritation of the disordered tissue. Vigorous irritation byapplicator 210 of the disordered tissue may be alternatively followed byleaving applicator 210 in place like a sterile adhesive bandage.

FIG. 4 depicts another applicator at 310 in an elevational side viewwhich may be used in an alternative embodiment of the present invention.The applicator or cotton swab depicted at 310 has a swab agitation pad312 upon a stem 314. Stem 314 may be formed from any suitable material,however, it is preferably relatively rigid to enable agitation pad 312to be pushed and/or moved in the desired manner. Pad 312 is preferablyused such that the side thereof is pushed against the disordered tissueand not the bulbous tip. The side is used so that sufficient pressurecan be applied while using the tip presents certain difficulties. Moreparticularly, when significant pressure is applied, the bulbous tip islikely to dig into the disordered tissue while the surrounding areareceives less pressure. Additionally, use of the bulbous tip results ina smaller surface area being contacted which may require agitatingdifferent portions sequentially.

It is preferable that the use of swab agitation pad 312 be used undersubstantially sterile conditions so as to not introduce pathogenicelements into the treatment site of the disordered tissue. The sterileagitation pad of the swab may be dipped into the inventive compositionand then used to abrade the skin. More preferably, the swab is held in abag as shown at 330 which also holds a burst pouch as shown at 340.Burst pouch 340 holds the treatment composition and is sized and/orpositioned within the bag such that upon bursting it saturates thecotton swab. An example of a bag holding a swab and a burst pouchdesigned to be frangible is disclosed in U.S. Pat. No. 5,709,866 toBooras, which was previously referenced.

An applicator and a burst pouch may also be held in separatecompartments of a bag such as bag 330 with a perforated divider.Similarly, an applicator and a frangible reservoir such as frangiblereservoir 14 may be held in separate compartments. The advantage of thisarrangement is that the burst pouch or frangible reservoir can beruptured to enable the treatment composition to flow into contact withapplicator. When a frangible glass reservoir is used, the perforationprevents glass from contacting the applicator.

Fibers such as cotton are not preferred for holding the treatmentcomposition while agitating the disordered tissue as extended exposureto cotton appears to reduce the efficacy of the methodology.Accordingly, when swab agitation pad 312 is formed from cotton, it ispreferred that the pad not be stored in contact with the treatmentcomposition. The use of a container such as burst pouch 340 when swabagitation pad 312 is formed from cotton achieves this objective.Applicators such as a swab may be stored in the same container as thetreatment composition when swab agitation pad 312 is formed fromsynthetic materials, naturally occurring fibers which do not reduce theefficacy of the methodology, or fibers such as cotton which have beenappropriately treated. Examples of suitable fibers include thosediscussed above in reference to applicator 10. Examples of a single bagor container for holding a swab are disclosed in U.S. Pat. No. 5,704,906to Fox and U.S. Pat. No. 4,952,204 to Korteweg which were bothpreviously referenced. Note that bag 330 and burst pouch 340 may beformed from any suitable materials and in any suitable manner.

Due to the relatively smooth texture of the cotton portion of mostconventional swabs, when such swabs are used it is typically necessaryto apply much more pressure than when an applicator such as applicator10 or 210 is utilized. Additionally, an applicator such as applicator 10is further preferred as applicator 10 enables the treatment compositionto be continuously delivered without requiring rewetting as a swab may.Further, swab agitation pad 312 holds only small quantities of thetreatment composition so it is necessary to rewet it in order to deliverlarge volumes of the treatment composition. This prevents swab agitationpad 312 from rapidly delivering large quantities of the treatmentcomposition.

The swab agitation pad may be replaced with a sponge to agitatedisordered tissue. An example of a foam pad or sponge mounted on a sticksuch as stem 314 is disclosed in U.S. Pat. No. 4,887,994 to Bedfordwhich was previously incorporated. Reference is made in U.S. Pat. No.4,887,994 at column 2, lines 44-46 to coarse foam pads, such coarse foampads are preferred for use as an agitation pad in accordance with thepresent invention. Coarse foam pads enable the disordered tissue to bemore easily agitated through combined rubbing and application of anappropriate amount of pressure than softer foam pads. The coarse foampad may also be utilized with a stick or stem.

Like the swab shown at 310, the other embodiments discussed above may bestored and used in a similar manner. More particularly, the coarse foampad on a stick, the coarse foam pad alone, or a towelette may be held ina bag or other sterile container such as is shown at 330 along with aburst pouch as shown at 340. Additionally, these applicators may be heldin a bag such as bag 330 without a burst pouch 340 in a dry sterilecondition for dipping into a separate reservoir of the treatmentcomposition or the treatment composition may be held in the bag alongwith the applicator.

FIG. 5 is an elevational perspective view of an alternative applicatorthat includes a fingertip applicator 410. Fingertip applicator 410includes an absorbent, agitation pad 412 held on an adhesive surface 414that the individual being treated or the medical professional applies tothe fingertip. Agitation pad 412 may include an absorbent material forretaining the treatment composition and it may alternatively containfixed abrasive elements to assist in the vigorous irritating of thedisordered tissue at the treatment site.

FIG. 6 is an elevational cross-section view of an alternative applicatorthat includes a finger- or digit-container applicator 510.Digit-container applicator 510 includes an absorbent, agitation pad 512with a first side 512 that acts as the agitation pad 516, and a secondside 514 that acts at the support 514. The user may rupture thecontainer 516 such as by tearing a slit 518 and inserting a finger intoapplicator 510 against second side 514. Container 516 is a bag like thatshown at 330 and may be referred to as what is commonly called a pillowpouch or package. Container 516 may also contain a burst pouch such asburst pouch 340. Applicator 510 is, however, preferably pre-moistened bythe presence of treatment composition 522 within container 516.Applicator may also be held in a container 516 in a dry sterilecondition for dipping into a separate reservoir of the treatmentcomposition.

First side 512 is made of an absorbent and abrasive material that issubstantially uniform in relation to the size of a disordered tissuesite. First side 512 preferably has the approximate roughness of aconventional gauze bandage or terry cloth. However, first side 512and/or second side 512 are not necessarily formed from cotton. In fact,as discussed above, cotton is preferably not used unless it has beenappropriately treated not to absorb the treatment composition,particularly the benzalkonium chloride.

Preferably, first side 512 is seamless and devoid of fabric folds etc.Additionally, where second side 514 is used to interface with a finger,it is a support for first side 512 as the agitation pad and deliveryportion of applicator 510. As a structural explanation of applicator510, if applicator were to be turned inside-out, first side 512 would beunder compressive stress and second side would be under tensile stress.

Like the other applicators, applicator 510 can have varying sizesdepending on its intended use. For example, if applicator 510 is used todeliver the treatment composition to a cold sore then it is large enoughto enable at least one fingertip into it. However, if applicator 510 isused to treat the sores caused by shingles on, for example, anindividual's back or other large surface of the body then it may beuseful for applicator 510 to be large enough so that several fingers oreven the entire hand can fit inside it like a mit. Such a mit sizedapplicator enables the treatment composition to be rapidly delivered tolarge surface areas.

FIG. 7 depicts another embodiment of a system for delivering a treatmentcomposition to disordered tissue. Like the mit sized version ofapplicator 510, applicator 610 is very useful for treating largesurfaces of the body such as a patient's back. Applicator 610 comprisesonly four main components: the treatment composition that is containedin a large frangible ampule 614 or reservoir, the container 616 and pad612 hold frangible ampule 614 in place.

Container 616 has thin-walls at recess 618, the closed end opposite fromopen delivery end 617, into which frangible ampule 614 is positioned.When applicator 610 is ready for use, handle wings 620 are squeezeduntil they compress the thin sidewalls of container 616 inward at recess618 such that pressure is applied to frangible ampule 614 such thatampule 614 ruptures. The treatment composition is then released andflows into pad 612.

Frangible ampule 614 preferably contains a volume of the treatmentcomposition ranging from about 0.5 ml to about 4 ml. The volumepreferably ranges from about 1.5 ml to about 3 ml and more preferablyabout 2 ml to about 3 ml.

Pad 612 is adhered to the rim of open delivery end 617 of container 616through any suitable means such as an adhesive, heat fusion, or amechanically interlocked configuration. Pad 612 prevents shards from therupture ampule from passing through and causing injury. Once pad 612 isadequately moistened then it can be used to rapidly apply the treatmentcomposition to large surface areas as shown in FIG. 8. FIG. 8 depictsthe use of applicator 610 to apply the treatment composition to apatient's chest afflicted with sores from shingles.

Applicator 610 can be used to merely deliver the treatment compositionwithout any vigorous agitation. Applicator 610 can also be used to applypressure and/or scrub the surface area to which the treatmentcomposition is being or has been delivered. Note that abrasiveness ofpad 612 can be varied significantly to achieve varying degrees ofability to vigorously agitate the disordered tissue. Another example ofan applicator that has a container that also acts as a handle, a glassampule positioned in the handle and a porous pad is disclosed in U.S.Pat. No. 4,183,684. U.S. Pat. No. 4,183,684 is hereby incorporated byreference. Not only are such applicators are able to deliver thetreatment composition to large surface areas of the body, it isdelivered rapidly in large quantities without requiring rewetting.

FIGS. 9-11 depict a towelette being used as an applicator to treatvarious disordered tissue. The towelettes depicted at 710 may be arelatively smooth towelette or a relatively abrasive towelette, thetowelettes can also have varying thicknesses. Towelettes are generallynot as useful as other applicators in treating disordered tissue as theyrequire a large quantity of the treatment composition in order to bewetted and yet deliver only a small quantity of the treatmentcomposition to the disordered tissue. However, the ability to hold agreater volume of the treatment composition can be increased byincreasing the thickness of the towelette. Additionally, the towelettecan be repeatedly dipped to rewet it. For example, FIG. 9 depicts a userwith a finger wrapped in a towelette that is being used to deliver thetreatment composition to a cold sore on the user's lip. The user canthen rewet only the portion of towelette 710 being used to applypressure to the cold sore.

Note that while it is less effective to use a towelette as compared withan applicator such as applicator 10 since the towelette cannot be usedto rapidly deliver a large volume of the treatment composition it canstill serve several functions. As discussed above, a towelette may beused to preclean the disordered tissue or to deliver an anesthetic.Precleaning disordered tissue with a towelette, especially an abrasivetowelette, may be useful to awaken the immune response for a synergisticeffect once the disordered tissue is vigorously agitated. The abrasivesurface towelette also has the advantage of removing tissue that is inthe process of sloughing off from the disordered tissue site. Suchtissue may provides a hindrance to the inventive method because itrestricts penetration of the anti-infective active agent to livingdisordered tissue.

The towelette may be used to deliver the treatment composition even ifit is not as effective as applicators used to rapidly delivering a largequantity of the treatment composition. A smooth towelette is generallyineffective in rubbing the disordered tissue as it has inadequateroughness to agitate the disordered tissue by rubbing it, however, itcan be used to push against the disordered tissue. For example, iftowelette 710 is relatively smooth then the user shown in FIG. 9 may dabthe cold sore with the treatment composition soaked towelette or theuser may apply pressure to the cold sore. Use of a towelette that has athickness and smoothness that is comparable to that of ordinaryhandwipes may be scrunched in order to better hold the towelette whiledabbing the disordered tissue and to concentrate the moisture held inthe towelette. Such a scrunched smooth towelette may result in folds, soit should not be rubbed against the disordered tissue as it may dig intothe disordered tissue, particularly if it is an open sore. In any event,folds resulting from drawing the towelette together prevent thetowelette from being used to uniformly agitate disordered tissue throughrubbing. If a towelette is be rubbed against the disordered tissue, thenit is preferable to use an abrasive towelette.

As indicated above, the abrasive towelettes are distinguished fromconventional towelettes used for cleaning hands, etc. In addition tobeing too smooth, conventional towelettes are also typically too thin tohold adequate amounts of moisture while an abrasive towelette preferablyhas sufficient thickness to hold adequate amounts of the treatmentcomposition. Of course, smooth towelettes with increased thickness canalso be used. The abrasive towelettes can also have increased thicknessto hold more treatment composition.

The towelette fiber may be formed from fibers such as those discussedabove in reference to applicator 10 or any of the other applicators. Thetowelette may be selected from existing stock formed from treatednatural fibers, synthetic fibers, and untreated natural fibers. Oneexample of an abrasive towelette is a rough paper towel used in thepaper towel industry or the like. One of ordinary skill in the art mayselect a towelette that has the preferred abrasive qualities whilemaintaining a preferred absorbability in order to convey theanti-infective active agent to the disordered tissue treatment site.

FIG. 10 depicts towelette 710 being used in the genital area. Anadvantage of using a towelette for delivering the treatment compositionin the genital area is that the towelette is able to conform to thevarious surface features and it enables the user to deliver thecomposition with sensitivity to the more sensitive parts in the genitalarea of the body. As with the other applicators, the towelette isdisposed of after a single use to prevent the spread of substancescontained in the disordered tissue.

FIG. 11 depicts towelette 710 being used to deliver the treatmentcomposition to a patient that has sores from shingles on his chest.Since the skin on body parts such as the chest, arms, the back, etc. arethicker than it is on the lips, use of a towelette is especially lesseffective than use of an applicator such as applicator 610. It mayhowever be useful to preclean the disordered tissue in this manner.Essentially, towelettes are primarily ideal for areas of the body thathave surfaces areas that are not primarily flat or that have irregularsurfaces such as the genital area. The towelette is ideal for theseareas as it can access all areas without causing pain.

The towelette may be held in a bag such as the bag shown at 330 whichalso holds a burst pouch as shown at 340. Burst pouch 340 holds thetreatment composition and is sized and/or positioned within the bag suchthat upon bursting it saturates the towelette. The bag may hold thetowelette and the burst pouch in a similar fashion to the designsdisclosed in U.S. Pat. No. 5,709,866 to Booras, which was previouslyreferenced. The towelette and a burst pouch may also be held in separatecompartments of a bag such as bag 330 with a perforated divider.Depending on the material used to form the towelette, it may beadvantageous to either separately store the towelette and the treatmentcomposition, as discussed above, or to store them together in the samecontainer, especially when the towelette is formed from syntheticmaterials. As discussed above, examples of a single bag or container forholding a towelette are disclosed in U.S. Pat. No. 5,704,906 to Fox andU.S. Pat. No. 4,952,204 to Korteweg which were both previouslyreferenced. Towelette 710 may be dipped into a separate reservoir andthen used to deliver the treatment composition.

The above embodiments comprise examples of an inventive method andsystem of treating disordered tissue. It is preferred not to dip a barefinger into a container of the treatment composition because oils orother materials contained on the finger may be of sufficient amount tocause the treatment composition to be rendered ineffective.Additionally, back contamination of composition in the container mayoccur. The agitation pads 12, 212, 312 412, 612 as well as first side512 are examples of a delivery and agitation means for delivering thetreatment composition and for agitating the disordered tissue of thepatient. Note that other examples include an abrasive towelette and acoarse foam pad. As discussed above, a conventional smooth towelette isnot an example of a delivery and agitation means capable of being usedto rub the disordered tissue.

The container 16 of applicator 10, the finger loop 228 of applicator210, the stem 314 of applicator 310 or similar applicators, the adhesivesurface 414, the second side 514 of applicator 510 and the container 616of applicator 610 are examples of a means for supporting the deliverymeans.

A coarse foam pad, pad 212, pad 412, fist side 512, pad 612 and abrasivetowelette 710 are all examples of delivery and agitation means capableof conforming to the surface features of the disordered tissue as thecorresponding supporting means also conforms to the surface features.Stated otherwise, the applicator is flexible such that both the deliveryand agitation means as well as the supporting means flex in conformancewith the surface anatomy of the disordered tissue. First side 512 isparticularly useful for adapting to the surface anatomy of thedisordered tissue. Pad 612 can also be thick enough to conform tovarious surfaces features of the body area being treated.

The frangible reservoir 14, container 216, container 516 and frangibleampule 614 are examples of a reservoir means for containing thecomposition. Additionally, a bottle or the like that contains treatmentcomposition 22 for use with applicator 310 is another example of areservoir means for containing the composition. Note that reservoir 14,container 216, container 516, and ampule 614 however, are configured tobe in fluid communication with the delivery and agitation means.Frangible reservoir 14, burst pouch 340 and frangible ampule 614 areconfigured to be in fluid communication with the delivery and agitationmeans once ruptured. Frangible reservoir 14 and frangible ampule 614 arefurther configured to continually deliver the treatment composition tothe delivery and agitation means while the delivery and agitation meansis agitating the disordered tissue until all of the treatmentcomposition has been delivered. Note that one of the primarydistinctions between frangible reservoir 14 as compared with burst pouch340 is that the frangible reservoir 14 is located within the container16. Similarly, frangible ampule 614 is located within container 616.

Container 516 and bag 330 are examples of container means for holdingthe applicator. This configuration, as discussed above, enables theapplicator to be held in a dry sterile condition for dipping into aseparate reservoir of the treatment composition. As also indicatedabove, container 516 and bag 330 can also hold the treatment compositionalong with the applicator such that the applicator is premoistened.Accordingly, container 516 and bag 330 are also examples of containermeans for holding the applicator and the treatment composition. Asfurther indicated above, container 516 and bag 330 can also hold thetreatment composition in a pouch along with the applicator. On thisbasis, container 516 and bag 330 are also examples of container meansfor holding the applicator and a reservoir means.

The inventive method of treating disordered tissue and the like includesimpregnating an applicator with the inventive anti-infective compositionand contacting the treatment site with the applicator. Vigorousagitation of the disordered tissue is particularly useful as the inducedphysical trauma causes the awakening of the body's immune response localto the irritation. As such, the immune response and the penetration ofthe inventive composition into the disordered tissue has the concertedeffect of a rapid decline of the infection.

Chemotaxis, the migration of phagocytes such as granular leucocytes andhuman leucocyte associated (HLA) antigens to an area of a tissuedisorder, is enhanced and assisted in the present invention by thevigorous agitation of the disordered tissue with the anti-infectiveactive agent or agents. The combination of the anti-infective activeagent, preferably benzalkonium chloride, with the chemotaxis phenomenoncaused by the vigorous agitation of the disordered tissue, has thesurprising effect of a rapid decline of the infectant such as a virus ora microbe in the disordered tissue. Note that one type of granularleucocyte, the neutrophil, has the ability to activate defenses whichare amino acids that exhibit a broad range of antibiotic activityagainst bacteria, fungi, and viruses. Consequently the synergisticeffect of vigorous agitation is rapid delivery and the awakening of theimmune response. The neutrophil, if activated is therefore useful totreat disordered tissue according to the present invention wherebacteria, fungi, or virus infections occur. Further, agitation causesfluids to concentrate in the area of the disordered tissue which furtherenables the active agent to move as needed in order to penetrateeffectively.

Other immune responses may occur with the vigorous agitation of thedisordered tissue site by the inventive method, and the inventors do notwish to be bound to any single theory that may explain the surprisingefficacy of the inventive method and system.

EXAMPLES OF THE PREFERRED EMBODIMENTS

The following examples are provided as illustrative of the inventivemethod and system. These examples are not intended to be limiting of theinvention. The examples all produce clinically discernable improvementof disordered tissue. By “clinically discernable improvement ofdisordered tissue,” it is understood that various testing methods may beused to quantify improvement of disordered tissue. One example ofclinically discernable improvement of disordered tissue includearresting the normal progression of a tissue disorder such as a coldsore. Another example of clinically discernable improvement ofdisordered tissue is healing of a tissue disorder at a faster rate thanwas observed before in a recurrent disorder such as a cold sore. Anotherexample of clinically discernable improvement of disordered tissue is anarrest of pain usually associated with the progression of a tissuedisorder such as a cold sore. Another example of clinically discernableimprovement of disordered tissue is the permanent deactivation of arecurrent tissue disorder site after the inventive method is applied toa disordered tissue site.

The clinical examples provide hereinbelow were performed with atreatment composition which included benzalkonium chloride. The carrierwas 30% by volume water and 70% isopropyl alcohol by volume of thecarrier. The treatment composition was prepared with about one partbenzalkonium chloride to about 750 parts carrier. More particularly, 5drops of benzalkonium chloride having a concentration of about 17% inisopropyl alcohol were added for each ounce of the carrier. The resultwas a treatment composition containing about 0.0133% benzalkoniumchloride by volume of the treatment composition. Although additives andother constituents may be combined with the mixture as set forth abovethese particular test treatment compositions did not include anyadditives.

As discussed above, the methodology in the examples includes vigorouslyapplying the composition to the disordered tissue and removing thesuperficial lipids by the carrier. The carrier also is useful for thepenetration of the disordered cells at the tissue disorder site. Eitherfollowing or simultaneously with the penetration of disordered cellswith the composition at the tissue disorder site, vigorous agitation ofthe tissue with the composition is carried out under conditions toincrease the flow of intercellular fluid to the tissue at the tissuedisorder site. This enables the active agent greater ease oftransportation at the site to better penetrate.

CLINICAL EXAMPLES Clinical Example 1

A male was diagnosed with several vesicles beginning to coalesce on thelip. Treatment was initiated immediately. After about 1 day, it wasobserved that the vesicles had not coalesced further and thatprogression of the cold sore through its normal stages was arrested.After about two days, scab tissue was observed to be sloughing off.After about seven days, no sign was left of the disordered tissue. Thepatient observed that for previous eruptions the complete healing ofthis cold sore at this site took from about two to three weeks.

Clinical Example 2

A male was diagnosed with a cold sore erupting below the corner of themouth. The usual tingling and tightening sensation that occurs with acold sore onset was observed by the patient. The inventive compositionand method was applied to the patient according to the inventive method.Immediately upon application, the usual tingling and tighteningsensation was not noticed. After about two days, no visible sign of acold sore was observable.

Clinical Example 3

A male with a history of cold sores ranging in a size from about 1.5 cmto about 2.5 cm in diameter was treated immediately upon sensing thetingling and tightening of an oncoming cold sore. A numbing sensationwas immediately noticed and the pain was gone. After about 3 days, thecold sore had begun to heal.

Clinical Example 4

A female was diagnosed with pustules and vistules upon the lower lip.The inventive composition was applied to the patient according to theinventive method, and pain was gone as soon as the application of theinventive composition was done. Instead of the normal weeping andscabbing the patient was used to, the cold sore healed without weepingor scabbing, and pain was minimal in comparison to previous experiences.

Clinical Example 5

A female had a disordered tissue eruption upon a digit with about 7vistules in the pre-eruption stage. The blistering typical of this typeof tissue disorder began to fade immediately after application of theinventive composition. A small amount of scaling was observed afterabout 2 weeks. The patient observed that the normal course of aneruption and healing at this cold sore site was shortened by theinventive composition and method.

Clinical Example 6

A female was diagnosed with a cold sore taking up about one-half of thearea of the lower lip. The cold sore had multiple lesions. The inventivecomposition was vigorously applied to the cold sore. Pain wasimmediately relieved and weeping was immediately arrested from the coldsore.

Clinical Example 7

A female observed tingling and tightening upon the inside of her lip inthe evening and observed one small pustule and three to four vistules atthe time of treatment the next morning. The inventive composition wasapplied by vigorous rubbing with a cotton swab. A second treatment wascarried out that evening, and a third treatment was carried out thefollowing morning. The pain was observed to be relieved fairly quicklyupon the first treatment. The patient observed that the inventivecomposition and method worked at least as well as her usual Zovirax®prescription, manufactured by Glaxo Wellcome Inc. of Research TrianglePark, N.C. The following advantages of the inventive composition andmethod were observed in comparison. One advantage was that fewerapplications were required. Additionally, no unpleasant tasting ointmentremains upon the lip during the treatment time.

Clinical Example 8

A female with a cold sore history including at least one eruption permonth was diagnosed with some yellow scabbing present upon a cold soresite. After vigorous irritation of the disordered tissue with theinventive composition, the patient observed that pain was completelygone after about seven hours.

Clinical Example 9

A male was diagnosed with a cold sore upon the lower lip. The inventivecomposition was applied by rubbing. The cold sore was observed to behealed after two days.

Clinical Example 10

A male was diagnosed with a number of cold sores at the corner of themouth and above the lip. Prior to vesicular eruption, the usual painthat precedes the eruption of a cold sore was observed about 24 hourspreviously. The inventive composition was applied by rubbing. Growth ofthe disordered tissue was immediately arrested and the tissue appearedto have cleared in three days following the treatment.

Clinical Example 11

A female diagnosed with a cold sore upon the chin about half way betweenthe base of the chin and the lower lip. The inventive composition wasapplied with rubbing. The cold sore was observed to have healed withinabout two days.

Clinical Example 12

A six year old female was diagnosed with an open cold sore upon thelower lip. The inventive composition was applied by vigorous rubbing.The cold sore was barely observable in about three days.

Clinical Example 13

A male was diagnosed with a cold sore upon the lower lip. The inventivecomposition was applied by vigorous rubbing. The progression of the coldsore was arrested and pain was stopped within a few minutes.

Clinical Example 14

A female was diagnosed with a cold sore at the corner of the mouth thatwould crack when the mouth was opened. The inventive composition wasapplied by vigorous rubbing. Within about two days, the cold sore wasobserved to be completely healed. The patient observed that cold soresin the corner of the mouth of this type usually took at least 7 to 10days to heal.

Clinical Example 15

A three-year old male was diagnosed with a cold sore upon the lip. Theinventive composition was applied by vigorous rubbing. It was observedthat progression of the cold sore was immediately arrested and that thecold sore did not form at that site again. The patient had about sixsites that erupted upon the lips frequently, and no treated sitere-erupted after treatment.

Clinical Example 16

A four-year old male with a history of about 25 oral cold sores wastreated by vigorous agitation of the disordered tissue upon are-eruption of each untreated cold sore. Pain was observed to ceaseimmediately upon treatment. Additionally, the cold sore did not eruptagain at any of the specific treatment sites even after a year.

Clinical Example 17

A male was diagnosed with a cold sore below the corner of the lower lip.The inventive composition was applied by vigorous rubbing. Immediatelyupon application, the tingling sensation that accompanied the cold sorewas gone. The next morning the cold sore had closed and was scabbed andhealing. Within two days of the application, the cold sore wascompletely healed. The patient observed that normal healing time, beforethe inventive treatment, took about two weeks.

Clinical Example 19

A male was diagnosed with a cold sore in the vistial stage upon thelower lip. The inventive composition was applied by vigorous rubbing.The cold sore was observed not to progress beyond the vistial stage.Healing occurred without pain and throbbing. The cold sore was totallyhealed within seven days.

Clinical Example 20

A female was diagnosed with two cold sores upon the lower lip. Theinventive composition was applied by vigorous rubbing between about 30and about 60 seconds. No pain was felt after the vigorous rubbing. Twodays later, one of the cold sores was gone and the other one had aslight scab that was also gone after three more days.

Clinical Example 21

A female was diagnosed with a cold sore that was about 2 cm across andgenerally round in shape, below one corner of the lower lip. Theinventive composition was applied by vigorous rubbing. The patientdescribed the cold sore to be burning and weeping. Within about oneminute of treatment, the burning had stopped. Within hours, the weepingstopped and a normal or non-cold sore scab appeared. Within days, thecold sore was gone and healed. No re-occurrence of the cold sore wasobserved.

Clinical Example 22

A male was diagnosed with an extremely swollen, red and weeping coldsore above one eye. The inventive composition was applied by vigorousrubbing to the cold sore. The swelling and redness were reduced withinminutes of the treatment. By the next morning, the cold sore appeared tobe a normal or non-cold sore scab. Complete healing was observed afterabout four days.

Comparative Clinical Example 1

A female was diagnosed with a cold sore above the upper corner of theupper lip. The inventive composition was applied but only slight rubbingoccurred. Soap was used on the cold sore treatment site that evening.Although the cold sore formed a scab after about two days, a new coldsore erupted at that time above the existing scab and spread itself intothe scab.

Clinical Example 21

A female was diagnosed with a canker or ulcer. The inventive compositionwas applied by vigorous rubbing until blood was seen on the cotton swab.The patient observed that the canker was gone after only about two orthree days. When the patient was re-examined one week after thetreatment, there was no sign of the canker.

Clinical Example 22

A male was diagnosed with shingles in two eruptions; one upon the faceover the cheekbone and the other upon the back of the neck. Theinventive composition was applied by vigorous rubbing to the eruptionupon the face. Immediate reduction in discomfort was observed. Theredness also immediately began to fade. The patient used shaving soapthe same day following treatment and observed that the eruption on theface was returning. A second treatment was repeated in the same mannerand progress was again arrested. The treatment site was not contactedthe second time with any soap. The eruption on the face healedcompletely while the eruption on the back of the neck remained evenafter about four weeks. Treatment was carried out on the eruption on theback of the neck and the eruption was healed in a few days.

Clinical Example 23

A female was diagnosed with a rash of shingles across the midsectionabove and at the naval. The inventive composition was applied byextensive and vigorous rubbing for about 20 minutes. The progression ofthe rash was immediately arrested and no new outbreaks were observed.The rash had been growing from small spots into large sores.

Clinical Example 24

A number of patients with primary eruption cases were treated by theinventive method. It was observed that in each patient, there was noreoccurrence of cold sores, as is typical with untreated primaryoccurrences.

Clinical Example 25

An individual was diagnosed with what appeared to be a spider bite uponthe lower calf area of the leg from a Brown Recluse. A “bullseye”discoloration was observed at the bite location with a brown-red middleregion and a red circumferential region. The entire area affected by thevenom appeared to be about eight to about nine centimeters in diameter.The inventive composition was applied by vigorous rubbing. After anovernight wait following treatment, the discoloration was notobservable. A scab that formed at the center of the bite, fell off afterabout three days.

Other ways to evaluate the progression of the cold sore healing processinclude measuring the size of the cold sore and also the degree ofinflammation thereof. One such method of evaluation is colorimetry ofinflamed tissue that creates a color scale that has apparently healthytissue of the patient as the baseline, and ranks the inflamed color withsome external standard or that nominalizes the inflamed tissue such asbeing at a nominal red scale of 10. A “nominal red scale” is defined asassigning the tissue color a nominal 10; a nominal zero beingundisordered tissue of the same type for the specific patient.Clinically discernable improvement of inflamed tissue is defined asreducing in the nominal red scale within about 24 hours by as much asabout two or more on the nominal red scale of 10. With a disorderedtissue having substantially no clinically discernable improvement ofdisordered tissue, a red scale decrease of below about one or lesswithin 24 hours is observed.

Another method is the assay of eosinophils and other immune responsesubstances in the inflamed area before and after the inventive method oftreatment. Where the presence of eosinophils and the like increases bymore than about 10% within about one hour of the inventive method oftreatment, as opposed to less than about 10% increase in eosinophils andthe like with a control cold sore, a clinically discernable improvementhas occurred.

The following are hypothetical examples. These hypothetical examplesinclude treatment compositions utilizing organochlorides other thanbenzalkonium chloride. More particularly, these organochlorides include:benzethonium chloride, methyl benzethonium chloride, cetyl pyridiniumchloride, chloroxylenol, hexachlorophene, triclosan, chlorhexidine.Their chemical structures are also provided to show that a variety oforganochlorides which differ structurally may be utilized. Theseorganochlorides are also used at various concentrations. Additionally,different carriers are utilized.

EXAMPLE 1

In a first example, disordered tissue that has a redness of 10 of anominal red scale is subjected to the inventive method by impregnatingan applicator with about 0.02% benzalkonium chloride in isopropylalcohol composition. The impregnated applicator is then vigorouslyapplied to a labial disordered tissue for a time period of about 30seconds. During the application time period, about 0.2 ml of theinventive composition is absorbed into the patient's disordered tissue.The patient's disordered tissue is estimated to have an area of about0.5 cm². The patient's disordered tissue is then examined and is foundto have a decreased nominal red scale to about 6 after about 24 hoursand an increased eosinophil assay of about 40% before about one hour.

Comparative Example 1

In a first comparative example, an applicator with about 0.02%benzalkonium chloride in isopropyl alcohol is gently applied to adisordered tissue by dabbing such that substantially no pressure isapplied sufficient to depress the tissue against hard tissue that liesunderneath. The impregnated applicator is applied to a labial disorderedtissue for a time period of about 30 seconds. During the applicationtime period, about 0.1 ml of the inventive composition is absorbed intothe patient's disordered tissue. The patient's disordered tissue isestimated to have an area of about 0.5 cm². The patient's disorderedtissue is then examined and is found to have a decreased nominal redscale from 10 to about 9 after about 24 hours and an increasedeosinophil assay of about 5% before about one hour.

Comparative Example 2

In another example comparative to the first example, a disordered tissueis treated substantially the same as in the first example with theexception that only isopropyl alcohol is impregnated in the applicator.The patient's disordered tissue is examined after the treatment and isfound to have an unchanged nominal red scale score of 10 and anegligibly increased eosinophil assay. However, note that some reductionof redness occurs when just alcohol is used, especially when thedisordered tissue is an open sore, as the alcohol tends to wash awaytoxic material. The redness returns as does the pain as toxins continueto build up since the source of the infection has not been eliminated.Note also that in the United States, alcohol cannot be listed as anactive agent in the treatment of cold sores caused by herpes.

EXAMPLE 2

In a second example, all conditions are the same as in the first examplewith the following variations. An embodiment of the inventivecomposition is applied to a typical sterile bandage and left over thepatient's disordered tissue for about one hour. The sterile bandage maydouble as part of the applicator. The composition contains, in additionto about 0.02% benzalkonium chloride in isopropyl alcohol, about 5% of acomposition of lidocaine and prilocaine in about a 1:1 mixture. Afterthe one hour time period, the patient's skin is substantially numbed,and the applicator is vigorously rubbed into the disordered tissue forabout 30 seconds. The patient experiences significantly less pain thanthat experienced in the first example. The patient's disordered tissueis then examined and is found to have a decreased nominal red scale toabout 3 from a beginning of eight after about 24 hours and an increasedeosinophil assay of about 50% before about one hour.

Comparative Example 3

In a second comparative example, all conditions are the same as in thesecond example except that no agitation of the disordered tissue occurs.The patient again experiences a numbing sensation after contact of theinventive composition with the cold sore, but is found to have adecreased nominal red scale to about nine and an increased eosinophilassay of about 10% before one hour.

Comparative Example 4

In another example comparative to the second example, the applicator isimpregnated with the lidocaine: prilocaine mixture in isopropyl alcoholbut no benzalkonium chloride or any other active agent is included. Thepatient's disordered tissue is then examined and is found to have anominal red scale of about nine and a negligibly increased eosinophilassay before one hour.

EXAMPLE 3

In a third example, a patient with pink eye is administered theinventive composition containing about 0.01% benzalkonium chloride in acarrier that is substantially nonirritating to the sclera and supportingeye tissue. The patient, with washed and disinfected hands, then rubsthe closed eyelid with the hand or fingers for about 30 seconds. Thepatient's eye is then examined and is found to have a decreased nominalred scale to about 1 after about 24 hours.

Comparative Example 5

In a third comparative example, a patient is treated exactly as in thethird example except that no rubbing through the closed eyelid iscarried out. The patient's eye is then examined and is found to have adecreased nominal red scale only to about 7 after about 24 hours.

Comparative Example 6

In another comparative example to the third example, the patient withpink eye is administered with a carrier but with no active agenttherein. The patient's eye is then examined and is found to have adecreased normal red scale to about 8 after about 24 hours.

EXAMPLE 4

In this example, a treatment composition is formed with benzethoniumchloride as the active agent. Hereinbelow is the chemical structure ofbenzethonium chloride:

The treatment composition is applied to disordered tissue like that inExample 1 which has a redness of 10 or a nominal red scale. Thedisordered tissue was on the patient's back. Note that when thetreatment composition is applied to thicker sections of skin such asoccur on the back it is more difficult to penetrate than on thinnersections such as the lip or cheek. Accordingly when treating such thickskin portions, it is necessary to increase the active agentconcentration, rub and/or press harder, or agitate more frequently. Thetreatment composition includes about 0.01% benzethonium chloride inisopropyl alcohol. An applicator impregnated with the treatmentcomposition is then vigorously applied to a labial disordered tissue fora time period of about 30 seconds. During the application time period,about 0.2 ml of the inventive composition is absorbed into the patient'sdisordered tissue. The patient's disordered tissue is estimated to havean area of about 0.5 cm². The patient's disordered tissue is thenexamined after about one hour and is found to have reduced redness,which is however not as reduced compared to that achieved in Example 1.Similarly, the eosinophil assay is increased but not to the extent ofthat in Example 1 which used benzalkonium chloride.

EXAMPLE 5

In this example, a treatment composition is formed with methylbenzethonium chloride as the active agent. Hereinbelow is the chemicalstructure of methyl benzethonium chloride:

The treatment composition is applied to disordered tissue like that inExample 1 which has a redness of 10 or a nominal red scale. Thetreatment composition includes about 0.02% methyl benzethonium chloridein a carrier comprising about 70% isopropyl alcohol by volume of thecarrier and about 30% water. An applicator impregnated with thetreatment composition is then vigorously applied to a labial disorderedtissue for a time period of about 30 seconds. During the applicationtime period, about 0.2 ml of the inventive composition is absorbed intothe patient's disordered tissue. The patient's disordered tissue isestimated to have an area of about 0.5 cm². The patient's disorderedtissue is then examined after about one hour and is found to havereduced redness, which is however not as reduced compared to thatachieved in Example 1. Similarly, the eosinophil assay is increased butnot to the extent of that in Example 1 which used benzalkonium chloride.

EXAMPLE 6

In this example, a treatment composition is formed with cetyl pyridiniumchloride as the active agent. Hereinbelow is the chemical structure ofcetyl pyridinium chloride.

The treatment composition is applied to disordered tissue like that inExample 1 on a patient's arm which has a redness of 10 or a nominal redscale. The treatment composition includes about 2.0% cetyl pyridiniumchloride in a carrier comprising about 60% isopropyl alcohol by volumeof the carrier, about 30% water and 10% acetone. An applicatorimpregnated with the treatment composition is then vigorously applied toa labial disordered tissue for a time period of about 30 seconds. Duringthe application time period, about 0.2 ml of the inventive compositionis absorbed into the patient's disordered tissue. The patient'sdisordered tissue is estimated to have an area of about 0.5 cm². Thepatient's disordered tissue is then examined after about one hour and isfound to have reduced redness, which is however not as reduced comparedto that achieved in Example 1. Similarly, the eosinophil assay isincreased but not to the extent of that in Example 1 which usedbenzalkonium chloride.

EXAMPLE 7

In this example, a treatment composition is formed with chloroxylenol asthe active agent. Hereinbelow is the chemical structure ofchloroxylenol.

The treatment composition is applied to disordered tissue like that inExample 1 which has a redness of 10 or a nominal red scale. Thetreatment composition includes about 0.5% chloroxylenol in acetone. Anapplicator impregnated with the treatment composition is then vigorouslyapplied to a labial disordered tissue for a time period of about 30seconds. During the application time period, about 0.2 ml of theinventive composition is absorbed into the patient's disordered tissue.The patient's disordered tissue is estimated to have an area of about0.5 cm². The patient's disordered tissue is then examined after aboutone hour and is found to have reduced redness, which is however not asreduced compared to that achieved in Example 1. Similarly, theeosinophil assay is increased but not to the extent of that in Example 1which used benzalkonium chloride.

EXAMPLE 8

In this example, a treatment composition is formed with hexachloropheneas the active agent. Hereinbelow is the chemical structure ofhexachlorophene.

The treatment composition is applied to disordered tissue like that inExample 1 which has a redness of 10 or a nominal red scale. Thetreatment composition includes about 0.04% hexachlorophene in a carriercomprising about 80% isopropyl alcohol by volume of the carrier, about15% water and 5% cetyl alcohol. An applicator impregnated with thetreatment composition is then vigorously applied to a labial disorderedtissue for a time period of about 30 seconds. During the applicationtime period, about 0.2 ml of the inventive composition is absorbed intothe patient's disordered tissue. The patient's disordered tissue isestimated to have an area of about 0.5 cm². The patient's disorderedtissue is then examined after about one hour and is found to havereduced redness, which is however not as reduced compared to thatachieved in Example 1. Similarly, the eosinophil assay is increased butnot to the extent of that in Example 1 which used benzalkonium chloride.

EXAMPLE 9

In this example, a treatment composition is formed with triclosan as theactive agent. Hereinbelow is the chemical structure of triclosan.

The treatment composition is applied to disordered tissue like that inExample 1 which has a redness of 10 or a nominal red scale. Thetreatment composition includes about 0.01% triclosan in a carriercomprising about 60% methyl alcohol by volume of the carrier, about 30%water and 10% acetone. An applicator impregnated with the treatmentcomposition is then vigorously applied to a labial disordered tissue fora time period of about 30 seconds. During the application time period,about 0.2 ml of the inventive composition is absorbed into the patient'sdisordered tissue. The patient's disordered tissue is estimated to havean area of about 0.5 cm². The patient's disordered tissue is thenexamined after about one hour and is found to have reduced redness,which is however not as reduced compared to that is achieved inExample 1. Similarly, the eosinophil assay is increased but not to theextent of that in Example 1 which used benzalkonium chloride.

EXAMPLE 10

In this example, a treatment composition is formed with chlorhexidine asthe active agent. Hereinbelow is the chemical structure ofchlorhexidine.

The treatment composition is applied to disordered tissue like that inExample 1 which has a redness of 10 or a nominal red scale. Thetreatment composition includes about 0.03% chlorhexidine in methylalcohol. An applicator impregnated with the treatment composition isthen vigorously applied to a labial disordered tissue for a time periodof about 30 seconds. During the application time period, about 0.2 ml ofthe inventive composition is absorbed into the patient's disorderedtissue. The patient's disordered tissue is estimated to have an area ofabout 0.5 cm². The patient's disordered tissue is then examined afterabout one hour and is found to have reduced redness, which is howevernot as reduced compared to that achieved in Example 1. Similarly, theeosinophil assay is increased but not to the extent of that in Example 1which used benzalkonium chloride.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrated andnot restrictive. The scope of the invention is, therefore, indicated bythe appended claims rather than by the foregoing description. Allchanges which come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

What is claimed and desired to be secured by United States LettersPatent is:
 1. A system for treating disordered tissue such as a coldsore treatment site, the system comprising: a treatment composition forapplication to and penetration into the disordered tissue, thecomposition comprising at least one anti-infective agent in a carrier,the at least one anti-infective agent comprising an organohalide,wherein the treatment composition is a liquid, said liquid comprising atissue penetrating component for penetrating skin in a rapid mannerwithout rapidly diffusing beyond the skin; and an applicator to deliverthe treatment composition into the disordered tissue.
 2. A system asrecited in claim 1, wherein the at least one anti-infective agentconsists essentially of the organochloride.
 3. A system as recited inclaim 1, wherein the at least one anti-infective agent comprises atleast one benzalkonium chloride compound.
 4. A system as recited inclaim 1, wherein the at least one anti-infective agent is selected fromthe group consisting of a benzalkonium bromide compound and cetyltrimethylammonium bromide.
 5. A system as recited in claim 1, whereinthe at least one anti-infective agent is selected from the groupconsisting of benzethonium chloride, methyl benzethonium chloride, cetylpyridinium chloride, chloroxylenol, hexachlorophene, triclosan, andchlorhexidine.
 6. A system as recited in claim 1, wherein the at leastone anti-infective agent is at least one quaternary ammonium chloridehaving an alkyl with 6-18 carbons.
 7. A system as recited in claim 1,wherein the at least one anti-infective agent comprises at least onebenzalkonium chloride compound at a concentration in the range fromabout 0.01% to about 0.5% by volume of the treatment composition.
 8. Asystem as recited in claim 1, wherein the carrier comprises isopropylalcohol.
 9. A system as recited in claim 1, wherein the carriercomprises water.
 10. A system as recited in claim 1, wherein the carriercomprises isopropyl alcohol and water.
 11. A system as recited in claim1, wherein the carrier consists essentially of isopropyl alcohol andwater.
 12. A system as recited in claim 1, wherein the carrier comprisesisopropyl alcohol and water, the water being in an amount ranging fromabout 20% to about 40% by volume of the carrier.
 13. A system as recitedin claim 1, wherein the carrier comprises an aqueous solution ofisopropyl alcohol at a concentration of about 70% by volume of thecarrier.
 14. A system as recited in claim 1, wherein the organohalidecomprises at least one benzalkonium chloride compound at a concentrationin the range from about 0.01% to about 0.5% by volume of the treatmentcomposition, and wherein the carrier comprises an aqueous solution ofisopropyl alcohol at a concentration of about 70% by volume of thecarrier.
 15. A system as recited in claim 1, wherein the carriercomprises at least one alcohol selected from the group consisting ofethanol, methanol, cetyl alcohol, and benzyl alcohol.
 16. A system asrecited, in claim 1, wherein the carrier comprises a compound selectedfrom the group consisting of acetone, acetic acid, acetic anhydride, andmixtures thereof.
 17. A system as recited in claim 1, wherein thetreatment composition is void of penetration inhibiting components. 18.A system as recited in claim 1, wherein the treatment compositionconsists essentially of the organohalide and the carrier.
 19. A systemas recited in claim 1, wherein the treatment composition and theapplicator are held within a container means for holding the applicator.20. A system as recited in claim 1, wherein the agitation pad is formedfrom synthetic fibers that have a mesh that enables the agitation pad tohold the treatment composition.
 21. A system as recited in claim 20,wherein the agitation pad comprises a folded sheet formed from a web offibers.
 22. A system as recited in claim 20, wherein the agitation padcomprises polyester fibers.
 23. A system as recited in claim 20, whereinthe agitation pad comprises a cluster of bristles.
 24. A system asrecited in claim 20, wherein said agitation pad has a delivery portionand wherein the delivery portion of the agitation pad has a length andsufficient rigidity for the agitation surface to scrub the disorderedtissue.
 25. A system as recited in claim 1, wherein the treatmentcomposition further comprises an anesthetic.
 26. A system as recited inclaim 1, further comprising: a topical anesthetic for application to thedisordered tissue before delivery of the treatment composition to thedisordered tissue to minimize pain experienced during delivery of thetreatment composition.
 27. A system for treating disordered tissue suchas a cold sore treatment site, the system comprising: a treatmentcomposition for application to and penetration into the disorderedtissue, the treatment composition comprising at least one benzalkoniumchloride compound in a carrier, wherein the carrier comprises a mixtureof isopropyl alcohol and water, wherein the treatment composition is aliquid, said liquid comprising a tissue penetrating component forpenetrating skin in a rapid manner without rapidly diffusing beyond theskin, and an applicator comprising: a reservoir for holding thetreatment composition, a flexible container around the reservoir forholding the reservoir in a manner such that compression of the flexiblecontainer causes the reservoir to release the treatment composition intothe flexible container, the flexible container having a closed endopposite to an open delivery end, and an agitation pad in the opendelivery end of the flexible container, wherein the agitation pad has aretention portion within the flexible container and a delivery portionthat extends beyond the open delivery end of the flexible container andwherein the delivery portion terminates at an agitation surface.
 28. Asystem as recited in claim 27, wherein the at least one benzalkoniumchloride compound concentration in the treatment composition is in therange from about 0.01% to about 0.5% by volume of the treatmentcomposition.
 29. A system as recited in claim 27, wherein the water iscomprised in an amount ranging from about 20% to about 40% by volume ofthe carrier.
 30. A system as recited in claim 27, wherein the water iscomprised in an amount ranging from about 20% to about 40% by volume ofthe carrier and the remainder of the carrier is comprised of isopropylalcohol.
 31. A system as recited in claim 27, wherein the carriercomprises an aqueous solution of isopropyl alcohol at a concentration ofabout 70% by volume of the carrier.
 32. A system as recited in claim 27,wherein the at least one benzalkonium chloride compound concentration inthe treatment composition is in the range from about 0.01% to about 0.5%by volume of the treatment composition, and wherein the carriercomprises an aqueous solution of isopropyl alcohol at a concentration ofabout 70% by volume of the carrier.
 33. A system as recited in claim 27,wherein the treatment composition is void of penetration inhibitingcomponents.
 34. A system as recited in claim 27, wherein the treatmentcomposition consists essentially of the at least one benzalkoniumchloride compound and the carrier.
 35. A system as recited in claim 27,wherein the carrier further comprises at least one alcohol selected fromthe group consisting of ethanol, methanol, cetyl alcohol, and benzylalcohol.
 36. A system as recited in claim 27, wherein the carrierfurther comprises a compound selected from the group consisting ofacetone, acetic acid, acetic anhydride, and mixtures thereof.
 37. Asystem as recited in claim 27, wherein the agitation pad is formed fromsynthetic fibers that have a mesh that enables the agitation pad to holdthe treatment composition.
 38. A system as recited in claim 27, whereinthe agitation pad comprises a folded sheet formed from a web of fibers.39. A system as recited in claim 27, wherein the agitation pad comprisesformed from polyester fibers.
 40. A system as recited in claim 27,wherein the agitation pad comprises a cluster of bristles.
 41. A systemas recited in claim 27, wherein the delivery portion of the agitationpad has a length and sufficient rigidity for the agitation surface toscrub the disordered tissue.
 42. A system as recited in claim 27,wherein the treatment composition further comprises an anesthetic.
 43. Asystem as recited in claim 27, further comprising: a topical anestheticfor application to the disordered tissue before delivery of thetreatment composition to the disordered tissue.
 44. A system fortreating disordered tissue such as a cold sore treatment site, thesystem comprising: a treatment composition for application to andpenetration into the disordered tissue, the composition comprising atleast one anti-infective agent in a carrier, said carrier comprising analcohol and water, wherein the at least one anti-infective agentcomprises an organohalide, wherein the treatment composition is a liquidthat is void of penetration inhibiting components, said liquidcomprising a tissue penetrating component for rapidly penetrating skinwithout rapidly diffusing beyond the skin, wherein the treatmentcomposition is substantially oil free such that there is essentially noresidue remaining that is visibly detectable to any substantial degreeafter the treatment composition has been applied and absorbed; and anapplicator comprising: a reservoir for holding the treatmentcomposition, a flexible container for holding the reservoir in a mannersuch that compression of the flexible container causes the reservoir torelease the treatment composition into the flexible container, theflexible container having a closed end opposite to an open delivery end,and an agitation pad at the open delivery end of the flexible container,wherein the agitation pad has a treatment composition delivery portion.45. A system as recited in claim 44, wherein the organohalide consistsessentially of at least one benzalkonium chloride compound and whereinthe carrier consists essentially of a mixture of isopropyl alcohol andwater.
 46. A system as recited in claim 44, wherein the delivery portionof the agitation pad is large enough to rapidly deliver the treatmentcomposition to a body part having a large surface area, such as the backor the chest, that is afflicted with a tissue disorder such as shingles.47. A system as recited in claim 1, wherein said applicator comprises: areservoir for holding the treatment composition, a flexible containeraround the reservoir for holding the reservoir in a manner such thatcompression of the flexible container causes the reservoir to releasethe treatment composition into the flexible container, the flexiblecontainer having a closed end opposite to an open delivery end, anagitation pad in the open delivery end of the flexible container suchthat the agitation pad receives the treatment composition upon releaseof said composition from the reservoir, wherein the agitation padcomprises a pad for holding the treatment composition until it isdelivered to the disordered tissue, wherein the agitation pad has aretention portion within the flexible container, and a delivery portionfor delivering the treatment composition to the disordered tissue,wherein the delivery portion extends beyond the open delivery end of theflexible container, wherein the delivery portion terminates at anagitation surface.
 48. A system as recited in claim 47, wherein saidreservoir is a frangible reservoir, and werein the flexible containerholds the frangible reservoir so that compression of the flexiblecontainer causes the frangible reservoir to rupture and release thetreatment composition.
 49. A system as recited in claim 1, wherein theat least one anti-infective agent consists essentially of at least onequaternary ammonium compound.
 50. A system as recited in claim 1,wherein said treatment composition is substantially oil free.
 51. Asystem as recited in claim 1, wherein said liquid has a viscosityapproximately equal to the viscosity of water.
 52. A system as recitedin claim 1, wherein said applicator includes delivery and agitationmeans for delivering the treatment composition and for agitating thedisordered tissue such that the treatment composition is simultaneouslydelivered as the disordered tissue is agitated.
 53. A system as recitedin claim 52, wherein the applicator further comprises means forsupporting the delivery means.
 54. A system as recited in claim 52,wherein the applicator further comprises means for supporting thedelivery means and reservoir means for containing the composition.
 55. Asystem as recited in claim 52, wherein the applicator includes reservoirmeans for containing the treatment composition, and wherein thereservoir means is frangible such that the treatment composition is influid communication with the delivery means and the agitation means whenthe reservoir means is ruptured.
 56. A system as recited in claim 52,wherein the applicator includes means for supporting the delivery meansand reservoir means for containing the treatment composition, whereinthe reservoir means is located within the supporting means, and whereinthe reservoir means is frangible such that the treatment composition isin fluid communication with the delivery and agitation means when thereservoir means is ruptured.
 57. A system as recited in claim 1, whereinthe system includes reservoir means for containing the treatmentcomposition, and wherein the applicator and the reservoir means are heldwithin a container means for holding the applicator and the reservoirmeans.
 58. A system as recited in claim 1, wherein the treatmentcomposition and the applicator are held within a container means forholding the applicator.
 59. A system as recited in claim 1, wherein saidorganohalide comprises at least one benzalkonium chloride compound. 60.A system as recited in claim 59, wherein said carrier comprises amixture of isopropyl alcohol and water.
 61. A system as recited in claim60, wherein the treatment composition further comprises an anesthetic.62. A system as recited in claim 1, wherein said organohalide comprisesat least one of alkylbenzyldimethylammonium chloride,alkyldimethyl/ethylbenzylammonium chloride,n-alkyldimethylbenzylammonium chloride,diisobutylphenoxyethoxyethyldimethylbenzylammonium chloride,n-(C₁₂C₁₄C₁₆)alkyl dimethylbenzylammonium chloride,didecyldimethylammonium chloride, dioctyldimethylammonium chloride,dialkyldimethylammonium chloride, dialkylmethylbenzylammonium chloride,octyldecyldimethylammonium chloride, lauryldimethylbenzylammoniumchloride, o-benzyl-p-chlorophenol, didecyldimethylammonium chloride,dioctyldimethylammonium chloride, andalkyl(C₁₄C₁₂C₁₆)dimethylbenzylammonium chloride.